Method for safely producing musk ketone
By performing the synthesis and nitration reaction of ketone musk in the silicon carbide microchannel reactor, the explosion risk and high cost problems in the traditional ketone musk production methods are solved, and a high yield, environmentally friendly and energy-saving ketone musk production is achieved.
Patent Information
- Application Number
- CN202411263170.9
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-09-10
- Publication Date
- 2024-12-13
AI Technical Summary
The traditional keto musk production methods have problems such as out-of-control reactions leading to explosion risk, complex process, many residues and high equipment requirements, and are costly, and lack safe, convenient and low-cost production methods.
The synthesis of ketone musk was carried out using silicon carbide microchannel reactor, and chlorotert-butane, 1,3-dimethyl-5-tert-butylbenzene and 2,6-dimethyl-4-tert-butylphenylethylene The ketone is gradually synthesized and nitration reaction is carried out in a silicon carbide microchannel reactor, combining continuous injection and efficient extraction to obtain a crude ketone musk product and obtain the finished product by recrystallization.
It significantly improves the yield of keto musk, eliminates the risk of explosion, reduces the cost of waste acid treatment, achieves environmentally friendly and energy-saving effects, and reduces raw material consumption and sewage treatment pressure.
Smart Images
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Figure BDA0005036368130000071
Abstract
Description
Technical Field
[0001] The invention relates to the technical field of musk ketone production, and more particularly to a method for safely producing musk ketone. Background Art
[0002] Musk ketone, namely 3,5-dinitro-2,6-dimethyl-4-tert-butylacetophenone, is an artificial musk that has not been found in nature so far and can only be synthesized artificially. It is mainly used to prepare flavors. Its aroma quality is more elegant than that of xylene musk and can be used as a fixative. It can be used to prepare cosmetics and as a soap flavor. It can also be used in combination with spices such as methyl violet copper, cinnamyl alcohol, and benzyl salicylate to prepare powdered flavors.
[0003] Traditional nitration is an intermittent reaction with a small heat exchange area and low heat transfer rate. If the heat of the reaction process cannot be transferred out in time during operation, the control limit of the cooling capacity will be reached, forming a vicious cycle. The reactants and products will decompose, generate a large amount of gas, and the pressure will rise sharply, which will eventually lead to material spraying, reactor damage, and even combustion and explosion. The danger of this reaction out of control can occur not only in the operating reactor, but also in other operating units and even in the storage process. In addition, the existing production method is complex and has many residues, and the equipment requirements are relatively high. There is an urgent need for a method for producing ketone musk that is easy to operate, highly safe, low-cost and high-conversion. Summary of the invention
[0004] In view of this, the present invention provides a method for safely producing ketone musk.
[0005] In order to achieve the above object, the present invention adopts the following technical solution:
[0006] A method for safely producing ketone musk comprises the following steps:
[0007] (1) Synthesis of tert-butyl chloride: tert-butyl alcohol and concentrated hydrochloric acid are placed in a reactor and stirred evenly. The mixture is stirred and reacted at room temperature. After the reaction is completed, the mixture is allowed to stand and the water layer is separated. The oil layer is first washed with water, dried, and then distilled. The fraction at 48-52° C. is collected to obtain tert-butyl chloride.
[0008] (2) Synthesis of 1,3-dimethyl-5-tert-butylbenzene: m-xylene and anhydrous aluminum chloride are added to a reactor for reaction. After the temperature of the reactant is cooled to 0°C, the stirrer is started and tert-butyl chloride is slowly added dropwise. Then, the mixture is stirred and reacted at 20-30°C for 5-6 hours. After the reaction is completed, the mixture is allowed to stand and the water layer is separated. The oil layer is washed with water and then with 5% sodium carbonate solution until it is neutral. After vacuum distillation, 1,3-dimethyl-5-tert-butylbenzene is obtained.
[0009] (3) Synthesis of 2,6-dimethyl-4-tert-butylacetophenone: 1,3-dimethyl-5-tert-butylbenzene, anhydrous aluminum chloride and dichloromethane are added to a reactor and stirred for reaction at 30-35°C, and acetic anhydride is added dropwise to the reactant. After the addition is completed, the reaction is continued at 60-70°C with stirring for 6-7 hours. After the reaction is completed, the mixture is allowed to stand, the water layer is separated, the oil layer is washed with water, and then washed with 10% sodium carbonate solution until neutral, the dichloromethane is recovered by atmospheric distillation, and then vacuum distillation is performed to obtain 2,6-dimethyl-4-tert-butylacetophenone;
[0010] (4) 2,6-dimethyl-4-tert-butylacetophenone and the mixed acid solution are continuously fed into the inlet of a silicon carbide microchannel reactor to carry out a nitration reaction. After the reaction is completed, the reaction product is extracted, dried, and crystallized into a light yellow powder to obtain a crude ketone musk product; the crude product is then recrystallized three times using a 95% ethanol solvent, and dried to obtain a finished ketone musk product.
[0011] Furthermore, in step (1), the mass volume ratio of the tert-butyl alcohol and concentrated hydrochloric acid is (1-2) g:(2-4) mL.
[0012] Furthermore, in step (1), the stirring speed is 1000-1500 rpm, the reaction time is 1-2 h; and the standing time is 6-7 h.
[0013] Furthermore, in step (2), the mass volume ratio of m-xylene to anhydrous aluminum chloride is (50-100) g:(1-2) mL.
[0014] Furthermore, in step (2), the mass ratio of the reactant to tert-butyl chloride is (1.5-2.0):1.
[0015] Furthermore, in step (3), the mass ratio of 1,3-dimethyl-5-tert-butylbenzene, anhydrous aluminum chloride and dichloromethane is (1-1.5):(2-3):(1.5-2).
[0016] Furthermore, in step (4), the mass volume ratio of the 2,6-dimethyl-4-tert-butylacetophenone and the mixed acid solution is (5-10) g: (1-5) mL.
[0017] Furthermore, in step (4), the mixed acid solution is a mixed solution of concentrated sulfuric acid and concentrated nitric acid, and the mass ratio of the concentrated sulfuric acid to the concentrated nitric acid is 1:(1.8-2.0).
[0018] Furthermore, in step (4), the injection flow rate of the mixed liquid is 5-10 mL / min, and the injection flow rate of the mixed acid solution is 2-8 mL / min; the reaction temperature in the silicon carbide microchannel reactor is 30-55°C, and the reaction residence time is 30-150s.
[0019] As an inventive concept identical to the above technical solution, the present invention also seeks protection for the ketone musk prepared by the above method.
[0020] It can be seen from the above technical solution that, compared with the prior art, the present invention discloses a method for safely producing ketone musk, with the following beneficial effects:
[0021] The invention adopts silicon carbide microchannel reaction to synthesize ketone musk, has the advantages of short reaction time, low reaction temperature, convenient operation, high yield and output, and can significantly improve the yield of ketone musk, which can be as high as 88.41%; the process completely eliminates the risk of explosion in the traditional intermittent kettle reaction nitration reaction, and continuously produces ketone musk with high output, greatly reduces the use of nitric acid, generates less waste acid, reduces the cost of subsequent waste acid treatment, saves a lot of raw material costs, reduces the pressure of later sewage treatment, and achieves the effect of environmental protection and energy saving.
[0022] In addition, the present application adopts a silicon carbide microchannel reaction method, which allows the reaction to occur at a smaller dose, further reducing the intensity of the reaction. The reactor made of carbon-silicon alloy has better thermal conductivity, which is conducive to rapid heat transfer of the reaction. The microchannel reaction method is continuous sampling, which can realize continuous reaction and improve reaction efficiency, thereby achieving large-scale production. DETAILED DESCRIPTION
[0023] The following will be described clearly and completely in conjunction with the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.
[0024] Example 1
[0025] A method for safely producing ketone musk comprises the following steps:
[0026] (1) Synthesis of tert-butyl chloride: 90 g of tert-butyl alcohol and 180 mL of concentrated hydrochloric acid were placed in a reactor and stirred evenly. The mixture was stirred and reacted at room temperature and 1000 rpm for 2 h. After the reaction was completed, the mixture was allowed to stand for 7 h. The water layer was separated and the oil layer was washed with water, dried, and then distilled. The fraction at 48° C. was collected to obtain tert-butyl chloride.
[0027] (2) Synthesis of 1,3-dimethyl-5-tert-butylbenzene: 50 g of m-xylene and 1 mL of anhydrous aluminum chloride were added to a reactor for reaction. After the temperature of the reactant was cooled to 0°C, the stirrer was started and mL of tert-butyl chloride was slowly added dropwise. Then, the mixture was stirred and reacted at 20°C for 6 h. After the reaction was completed, the mixture was allowed to stand and the water layer was separated. The oil layer was washed with water and then with 5% sodium carbonate solution until it was neutral. After vacuum distillation, 1,3-dimethyl-5-tert-butylbenzene was obtained.
[0028] (3) Synthesis of 2,6-dimethyl-4-tert-butylacetophenone: 10 g of 1,3-dimethyl-5-tert-butylbenzene, 20 g of anhydrous aluminum chloride and 15 g of dichloromethane were added to a reactor and stirred at 35°C for reaction. 10 mL of acetic anhydride was added dropwise to the reactant. After the addition was completed, the reaction was continued at 60°C for 7 h with stirring. After the reaction was completed, the mixture was allowed to stand and the water layer was separated. The oil layer was washed with water and then washed with 10% sodium carbonate solution until neutral. The dichloromethane was recovered by atmospheric distillation and then subjected to reduced pressure fractionation to obtain 2,6-dimethyl-4-tert-butylacetophenone.
[0029] (4) 50 g of 2,6-dimethyl-4-tert-butylacetophenone and 10 mL of a mixed acid solution (a mass ratio of concentrated sulfuric acid to concentrated nitric acid of 1:1.8) were continuously fed into the inlet of a silicon carbide microchannel reactor at injection rates of 5 mL / min and 2 mL / min, respectively, and the nitration reaction was carried out at 30° C. for 150 s. After the reaction was completed, the reaction product was extracted, dried, and crystallized into a light yellow powder to obtain a crude ketone musk product; the crude product was then recrystallized three times using a 95% ethanol solvent, and dried to obtain a finished ketone musk product.
[0030] Example 2
[0031] A method for safely producing ketone musk comprises the following steps:
[0032] (1) Synthesis of tert-butyl chloride: 180 g of tert-butyl alcohol and 450 mL of concentrated hydrochloric acid were placed in a reactor and stirred evenly. The mixture was stirred at room temperature and 1500 rpm for 1 h. After the reaction was completed, the mixture was allowed to stand for 6 h. The water layer was separated and the oil layer was washed with water, dried, and then distilled. The fraction at 50° C. was collected to obtain tert-butyl chloride.
[0033] (2) Synthesis of 1,3-dimethyl-5-tert-butylbenzene: 75 g of m-xylene and 1.5 mL of anhydrous aluminum chloride were added to a reactor for reaction. After the temperature of the reactant was cooled to 0°C, the stirrer was started and 17 mL of tert-butyl chloride was slowly added dropwise. Then, the mixture was stirred and reacted at 25°C for 5.5 h. After the reaction was completed, the mixture was allowed to stand and the water layer was separated. The oil layer was washed with water and then with 5% sodium carbonate solution until it was neutral. After vacuum distillation, 1,3-dimethyl-5-tert-butylbenzene was obtained.
[0034] (3) Synthesis of 2,6-dimethyl-4-tert-butylacetophenone: 12 g of 1,3-dimethyl-5-tert-butylbenzene, 25 g of anhydrous aluminum chloride and 17 g of dichloromethane were added to a reactor and stirred at 30°C for reaction. 10 mL of acetic anhydride was added dropwise to the reactant. After the addition was completed, the reaction was continued at 70°C for 6 h with stirring. After the reaction was completed, the mixture was allowed to stand and the water layer was separated. The oil layer was washed with water and then washed with 10% sodium carbonate solution until neutral. The dichloromethane was recovered by atmospheric distillation and then subjected to reduced pressure fractionation to obtain 2,6-dimethyl-4-tert-butylacetophenone.
[0035] (4) 75 g of 2,6-dimethyl-4-tert-butylacetophenone and 25 mL of a mixed acid solution (a mass ratio of concentrated sulfuric acid to concentrated nitric acid of 1:2.0) were continuously fed into the inlet of a silicon carbide microchannel reactor at injection rates of 10 mL / min and 8 mL / min, respectively, and a nitration reaction was carried out at 55° C. for 30 seconds. After the reaction was completed, the reaction product was extracted, dried, and crystallized into a light yellow powder to obtain a crude ketone musk product; the crude product was then recrystallized three times using a 95% ethanol solvent, and dried to obtain a finished ketone musk product.
[0036] Example 3
[0037] A method for safely producing ketone musk comprises the following steps:
[0038] (1) Synthesis of tert-butyl chloride: 90 g of tert-butyl alcohol and 270 mL of concentrated hydrochloric acid were placed in a reactor and stirred evenly. The mixture was stirred at room temperature and 1350 rpm for 1.5 h. After the reaction was completed, the mixture was allowed to stand for 6.5 h. The water layer was separated and the oil layer was washed with water, dried, and then distilled. The fraction at 52° C. was collected to obtain tert-butyl chloride.
[0039] (2) Synthesis of 1,3-dimethyl-5-tert-butylbenzene: 100 g of m-xylene and 2 mL of anhydrous aluminum chloride were added to a reactor for reaction. After the temperature of the reactant was cooled to 0°C, the stirrer was started and 20 mL of tert-butyl chloride was slowly added dropwise. Then, the mixture was stirred at 30°C for 5 h. After the reaction was completed, the mixture was allowed to stand and the water layer was separated. The oil layer was washed with water and then with 5% sodium carbonate solution until it was neutral. After vacuum distillation, 1,3-dimethyl-5-tert-butylbenzene was obtained.
[0040] (3) Synthesis of 2,6-dimethyl-4-tert-butylacetophenone: 15 g of 1,3-dimethyl-5-tert-butylbenzene, 30 g of anhydrous aluminum chloride and 20 g of dichloromethane were added to a reactor and stirred at 33°C for reaction. 10 mL of acetic anhydride was added dropwise to the reactant. After the addition was completed, the reaction was continued at 65°C for 6.5 h with stirring. After the reaction was completed, the mixture was allowed to stand and the water layer was separated. The oil layer was washed with water and then washed with 10% sodium carbonate solution until neutral. The dichloromethane was recovered by atmospheric distillation and then subjected to reduced pressure fractionation to obtain 2,6-dimethyl-4-tert-butylacetophenone.
[0041] (4) 100 g of 2,6-dimethyl-4-tert-butylacetophenone and 50 mL of a mixed acid solution (a mass ratio of concentrated sulfuric acid to concentrated nitric acid of 1:1.9) were continuously fed into the inlet of a silicon carbide microchannel reactor at injection rates of 7 mL / min and 5 mL / min, respectively, and the nitration reaction was carried out at 43° C. for 85 seconds. After the reaction was completed, the reaction product was extracted, dried, and crystallized into a light yellow powder to obtain a crude ketone musk product; the crude product was then recrystallized three times using 95% ethanol solvent, and dried to obtain a finished ketone musk product.
[0042] Comparative Example 1
[0043] Compared with Example 2, the difference is that the mixed acid solution in step (4) is replaced by sulfuric acid solution, and the rest remains unchanged;
[0044] Comparative Example 2
[0045] Compared with Example 2, the difference is that the dropwise addition of 20 mL of tert-butyl chloride and 10 mL of acetic anhydride in steps (2) and (3) is replaced by the dropwise addition of 30 mL of tert-butyl chloride and 20 mL of acetic anhydride;
[0046] Comparative Example 3
[0047] Compared with Example 2, the difference is that the injection flow rates of 2,6-dimethyl-4-tert-butylacetophenone and the mixed acid solution in step (4) are replaced with 12 mL / min and 10 mL / min, and the nitration reaction temperature is increased to 60°C;
[0048] Comparative Example 4
[0049] Patent No. CN104529731A discloses a method for preparing musk ketone in an efficient and mild manner, which uses pentadecane dicarboxylic acid as a raw material to prepare musk ketone through esterification reaction, alcohol-ketone condensation reaction, elimination reaction, and Michael addition reaction.
[0050] Test example
[0051] The content of ketone musk in the ketone musk crude products prepared by the methods of Examples 1-3 and Comparative Examples 1-4, as well as the yield of the ketone musk finished product after recrystallization and drying were determined by gas chromatograph, and the determination results are shown in Table 1.
[0052] Table 1 Content and yield of ketomusk generated by different methods
[0053]
[0054]
[0055] As can be seen from Table 1, the method of Examples 1-3 of the present invention can increase the content of ketone musk in the reaction product and the yield of ketone musk, among which the method of Example 2 has the best effect; Comparative Examples 1-3 change the flow rate, addition amount and reaction temperature of the sample in the preparation method, and the content and yield of ketone musk in the reaction product prepared by them are significantly lower than those of Examples 1-3. This is because the reaction in the preparation method is an exothermic reaction, and the reactants should be gradually mixed, and the addition ratio of the solvent should be strictly controlled, otherwise the yield and content of the product will be reduced; Comparative Example 4 is a method in the prior art, which can also increase the content and yield of ketone musk in the reactant, but the degree of increase is significantly lower than that of the composition of the present invention.
[0056] The various embodiments in this specification are described in a progressive manner, and each embodiment focuses on the differences from other embodiments. The same or similar parts between the various embodiments can be referenced to each other.
[0057] The above description of the disclosed embodiments enables one skilled in the art to implement or use the present invention. Various modifications to these embodiments will be apparent to one skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention will not be limited to the embodiments shown herein, but rather to the widest scope consistent with the principles and novel features disclosed herein.
Claims
1. A method for safely producing ketone musk, characterized in that: The following steps are involved: (1) Synthesis of tert-butyl chloride: tert-butyl alcohol and concentrated hydrochloric acid are placed in a reactor and stirred evenly. The mixture is stirred and reacted at room temperature. After the reaction is completed, the mixture is allowed to stand and the water layer is separated. The oil layer is first washed with water, dried, and then distilled. The fraction at 48-52° C. is collected to obtain tert-butyl chloride. (2) Synthesis of 1,3-dimethyl-5-tert-butylbenzene: m-xylene and anhydrous aluminum chloride are added to a reactor for reaction. After the temperature of the reactant is cooled to 0°C, the stirrer is started and tert-butyl chloride is slowly added dropwise. Then, the mixture is stirred and reacted at 20-30°C for 5-6 hours. After the reaction is completed, the mixture is allowed to stand and the water layer is separated. The oil layer is washed with water and then with 5% sodium carbonate solution until it is neutral. After vacuum distillation, 1,3-dimethyl-5-tert-butylbenzene is obtained. (3) Synthesis of 2,6-dimethyl-4-tert-butylacetophenone: 1,3-dimethyl-5-tert-butylbenzene, anhydrous aluminum chloride and dichloromethane are added to a reactor and stirred for reaction at 30-35°C, and acetic anhydride is added dropwise to the reactant. After the addition is completed, the reaction is continued at 60-70°C with stirring for 6-7 hours. After the reaction is completed, the mixture is allowed to stand, the water layer is separated, the oil layer is washed with water, and then washed with 10% sodium carbonate solution until neutral, the dichloromethane is recovered by atmospheric distillation, and then vacuum distillation is performed to obtain 2,6-dimethyl-4-tert-butylacetophenone; (4) 2,6-dimethyl-4-tert-butylacetophenone and the mixed acid solution are continuously fed into the inlet of a silicon carbide microchannel reactor to carry out a nitration reaction. After the reaction is completed, extraction is performed, and a light yellow powder is crystallized after drying to obtain a crude ketone musk product; the crude product is then recrystallized three times using a 95% ethanol solvent, and the finished ketone musk is obtained after drying.
2. The method according to claim 1, characterized in that In step (1), the mass volume ratio of the tert-butyl alcohol and concentrated hydrochloric acid is (1-2) g:(2-4) mL.
3. The method according to claim 1, characterized in that In step (1), the stirring speed is 1000-1500 rpm, the reaction time is 1-2 h, and the standing time is 6-7 h.
4. The method according to claim 1, characterized in that: In step (2), the mass volume ratio of m-xylene to anhydrous aluminum chloride is (50-100) g:(1-2) mL.
5. The method according to claim 1, characterized in that: In step (2), the mass ratio of the reactant to tert-butyl chloride is (1.5-2.0):
1.
6. The method according to claim 1, characterized in that In step (3), the mass ratio of 1,3-dimethyl-5-tert-butylbenzene, anhydrous aluminum chloride and dichloromethane is (1-1.5):(2-3):(1.5-2).
7. The method according to claim 1, characterized in that In step (4), the mass volume ratio of the 2,6-dimethyl-4-tert-butylacetophenone and the mixed acid solution is (5-10) g: (1-5) mL.
8. The method according to claim 1, characterized in that: In step (4), the mixed acid solution is a mixed solution of concentrated sulfuric acid and concentrated nitric acid, and the mass ratio of the concentrated sulfuric acid to the concentrated nitric acid is 1:(1.8-2.0).
9. The method according to claim 1, characterized in that: In step (4), the injection flow rate of the mixed solution is 5-10 mL / min, and the injection flow rate of the mixed acid solution is 2-8 mL / min; the reaction temperature in the silicon carbide microchannel reactor is 30-55° C., and the reaction residence time is 30-150 s.
10. A ketone musk prepared by the method according to any one of claims 1 to 9.