Preparation and refining method of ambergris

Abstract

The present application relates to the preparation and refining field of sun musk, and discloses a preparation method and a refining method of sun musk. The preparation method comprises the following steps: 1) methylation reaction: 6-tert-butyl-3-methyl phenol, dimethyl sulfate and lye are mixed in the presence of a catalyst, methylation reaction is carried out, and then solid-liquid separation is carried out, so that 3-methoxy-4-tert-butyl toluene is obtained; 2) nitration reaction: nitric acid and 3-methoxy-4-tert-butyl toluene are mixed in the presence of acetic anhydride under low-temperature conditions, nitration reaction is carried out, and then hydrolysis washing is carried out, so that sun musk is obtained. The method avoids the use of chloromethane with safety hazards in the existing process, and avoids the use of a strong acid system which has corrosion and damage to equipment, and sun musk is prepared under mild conditions. Moreover, the sun musk prepared by the preparation method can maintain high yield and purity.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of preparation and refining of musk ambrette, and discloses a preparation method and a refining method of musk ambrette. BACKGROUND

[0002] Musk ambrette is one of main raw materials for preparing perfume, etc. In the traditional process, 6-tert-butyl-m-cresol is often used as raw material, and 3-methoxy-4-tert-butyl toluene is obtained by reacting with chloromethane in the presence of a catalyst, and then the musk ambrette is obtained by reacting with concentrated sulfuric acid and nitric acid. In the above process, not only flammable and explosive chloromethane is used, but also concentrated sulfuric acid and nitric acid with strong oxidizing property and corrosive property are used, so that the safety cannot be guaranteed, and the yield and purity of musk ambrette are low. SUMMARY

[0003] The present application provides a preparation method and a refining method of musk ambrette to solve the technical problems of safety hazard in the process of preparing musk ambrette and low yield and purity of musk ambrette in the prior art.

[0004] In order to achieve the above-mentioned purpose, the present application provides a preparation method of musk ambrette, characterized in comprising the following steps:

[0005] 1) methylating reaction: 6-tert-butyl-3-methyl phenol, dimethyl sulfate and lye are mixed in the presence of a catalyst to perform methylating reaction, and then 3-methoxy-4-tert-butyl toluene is obtained by solid-liquid separation;

[0006] 2) nitration reaction: nitric acid and 3-methoxy-4-tert-butyl toluene are mixed in the presence of acetic anhydride under low temperature conditions to perform nitration reaction, and then musk ambrette is obtained by hydrolysis and washing.

[0007] In the present application, the catalyst in step 1) is tetrabutylammonium bromide and / or tetrabutylammonium chloride, and preferably tetrabutylammonium bromide.

[0008] In the present application, the lye is a mixture of alkali solution and tablet alkali. Specifically, the alkali solution is NaOH solution with a mass concentration of 20-40wt%. In the mixture, the mass ratio of alkali solution to tablet alkali is 4-5:1.

[0009] In the present application, the mass ratio of 6-tert-butyl-3-methyl phenol, dimethyl sulfate, lye and catalyst is 1:0.8-1.5:0.8-1.5:0.01-0.04.

[0010] In one specific embodiment of the present application, the methylating reaction comprises the following steps:

[0011] 1-1) mixing 6-tert-butyl-3-methylphenol, a catalyst and dimethyl sulfate at a first temperature to obtain a first mixture;

[0012] 1-2) performing a methylation reaction after adding a lye to the first mixture, and performing a solid-liquid separation to obtain 3-methoxy-4-tert-butyltoluene.

[0013] In the present application, in step 1-1), the first temperature is -10℃ to -15℃.

[0014] In the present application, in step 1-2), the dropping speed of the lye is controlled so that the temperature of the system is 35-38℃, and the dropping time is 3-5h; the time of the methylation reaction is 10-30min.

[0015] In the present application, the method further comprises a step of washing the 3-methoxy-4-tert-butyltoluene obtained in step 1-2) with water, preferably washing the 3-methoxy-4-tert-butyltoluene obtained in step 1-2) with water for more than 2 times.

[0016] In the present application, in step 2), the mass ratio of the 3-methoxy-4-tert-butyltoluene, the acetic anhydride and the nitric acid is 1:1.7-1.9:0.7-0.9.

[0017] In the present application, in step 2), the temperature of the low-temperature condition is 7℃-12℃.

[0018] In one specific embodiment of the present application, the nitration reaction comprises the following steps:

[0019] 2-1) under low-temperature conditions, 80-90wt% of acetic anhydride is introduced into a reaction kettle under stirring;

[0020] 2-2) performing a second mixing of the remaining acetic anhydride and the 3-methoxy-4-tert-butyltoluene to obtain a second mixture;

[0021] 2-3) after reducing the temperature to below -2℃, 40-50wt% of nitric acid is added into the reaction kettle at a first speed;

[0022] 2-4) while adding the remaining nitric acid into the reaction kettle at a second speed, the second mixture is added into the reaction kettle at a third speed to perform a nitration reaction.

[0023] In the present application, the second speed is less than the first speed. Specifically, the first speed is 5-10g / min, and the second speed is 1-4g / min.

[0024] In the present application, the second speed and the third speed are such that the temperature is -8℃ to -2℃. The specific value of the third speed is not particularly limited as long as the temperature satisfies -8℃ to -2℃.

[0025] In the present application, the method further comprises water washing the product obtained in step 2-4), preferably, the step of water washing comprises: mixing the product obtained in step 2-4) with water under the condition of -5℃ to 5℃, preferably 0℃, under the condition of stirring, washing, until the product is yellow or light yellow.

[0026] The second aspect of the present application provides a refining method of musk ambrette, characterized in that the method comprises the following steps:

[0027] S1, under the first stirring condition, mixing musk ambrette crude product, solvent oil, alkali and water, then water washing and removing the alkali solution;

[0028] S2, under the second stirring condition, filtering the product of step S1 after temperature reduction treatment to obtain a solid-phase product and a filtrate;

[0029] S3, heating the filtrate obtained in step S2 to remove solvent oil;

[0030] S4, mixing the product obtained in step S4 with the first ethanol, and then performing primary crystallization to obtain a primary crystallization product;

[0031] S5, mixing the primary crystallization product obtained in step S4 with the second ethanol, and then performing secondary crystallization to obtain a secondary crystallization product;

[0032] S6, drying the secondary crystallization product to obtain refined musk ambrette.

[0033] In the present application, in step S1, the step of water washing comprises: stirring for 10-20min under the condition of 75-80℃, and then standing for 10-30min.

[0034] In the present application, in order to further improve the purity of musk ambrette, preferably, the water washing is performed at least 2 times or more.

[0035] In the present application, the mass ratio of the musk ambrette crude product, the solvent oil, the alkali and the water is 1:4-8:0.05-0.08:1.4-2.

[0036] In the present application, the type of solvent oil is not particularly limited, and a conventional type of solvent oil in the art can be used, for example, the solvent oil is 120# solvent oil.

[0037] In the present application, in step S2, the temperature reduction treatment is such that the temperature is below 45℃.

[0038] In the present application, the filtrate obtained in step S2 is heated. The heating causes the solvent oil to volatilize and then be discharged from the system. Preferably, in order to save costs, the solvent oil volatilized and discharged by heating is condensed and returned to step S1.

[0039] In the present application, the steps of the first crystallization and the second crystallization each independently comprise: heating the product obtained in step S4 to 70-80℃, maintaining the temperature for 10-20 min, then cooling to 40-48℃, and then cooling to 18-28℃.

[0040] In the present application, through the twice crystallization process and crystallization according to the steps of the present application, the by-products and the like in musk ambrette can be sufficiently removed, and the purity of the purified musk ambrette can be improved.

[0041] In the present application, in order to make the by-products and the like in the crude musk ambrette sufficiently dissolved, preferably, the amount of the first ethanol and the second ethanol each independently is 2-4 times of the amount of the crude musk ambrette.

[0042] In the present application, the method further comprises: after the first crystallization and the second crystallization, respectively centrifuging the products after crystallization to remove the first ethanol or the second ethanol. Through the above steps, the purity of the purified musk ambrette can be further improved.

[0043] In the present application, the stirring in each step is not particularly limited, as long as the materials can be sufficiently mixed and uniform.

[0044] In one specific embodiment of the present application, as shown in Figure 1 a preparation method of musk ambrette is provided, wherein the method comprises:

[0045] I, methylation reaction: 6-tert-butyl-3-methylphenol, dimethyl sulfate and lye are mixed in the presence of a catalyst, a methylation reaction is carried out, and then solid-liquid separation is performed to obtain 3-methoxy-4-tert-butyltoluene;

[0046] II, nitration reaction: nitric acid and 3-methoxy-4-tert-butyltoluene are mixed in the presence of acetic anhydride under low temperature conditions, a nitration reaction is carried out, and then hydrolysis and washing are performed to obtain a crude musk ambrette;

[0047] III, refining:

[0048] III-1, under the first stirring condition, the crude musk ambrette obtained in step II, solvent oil, alkali and water are mixed, then water washing is performed, and then the alkali solution is removed;

[0049] III-2, after the product of step III-1 is subjected to the temperature reduction treatment under the second stirring condition, filtration is performed to obtain a solid-phase product and a filtrate;

[0050] III-3, the filtrate obtained in step III-2 is heated to remove the solvent oil;

[0051] III-4, the product obtained in step III-3 is mixed with the first ethanol, and after one-time crystallization, a one-time crystallization product is obtained;

[0052] III-5, the one-time crystallization product obtained in step III-4 is mixed with the second ethanol, and after two-time crystallization, a two-time crystallization product is obtained;

[0053] III-6, the two-time crystallization product is dried to obtain refined musk ambrette.

[0054] The method for preparing musk ambrette provided by the present application avoids the use of chloromethane which has safety hazards and the use of a strong acid system which has corrosion and damage to equipment, and musk ambrette is prepared under mild conditions. The musk ambrette prepared by the method has high yield and purity.

[0055] The method for refining musk ambrette provided by the present application realizes the refining of crude musk ambrette through water washing, multiple crystallization and other steps, improves the purity of the product after refining, and the refining method is simple and easy to industrialize. BRIEF DESCRIPTION OF DRAWINGS

[0056] ATTACHMENT Figure 1 The method for preparing musk ambrette and the refining method flowchart provided by the present application. EMBODIMENT

[0057] In order to enable personnel in the technical field to better understand the technical solutions in the present application, the technical solutions of the present application will be clearly and completely described below in combination with embodiments. Obviously, the described embodiments are only a part of the embodiments of the present application, and all other embodiments obtained by those skilled in the art without creative labor on the basis of the embodiments in the present application shall belong to the protection scope of the present application. EMBODIMENT

[0058] Methylation reaction

[0059] 1-1) Under stirring conditions, 600 kg of 6-tert-butyl-3-methylphenol, 15 kg of tetramethylammonium chloride and 540 kg of dimethyl sulfate are introduced into a reaction kettle, -10 to -15℃ chilled water is introduced into the jacket of the reaction kettle, and the temperature in the reaction kettle is controlled;

[0060] 1-2) 345 kg of a 30 wt% NaOH solution was mixed with 75 kg of 99 wt% flake caustic to obtain a lye (mass ratio of lye to flake caustic was 4.6:1), the lye was added dropwise into the reaction kettle to perform the methylation reaction, the dropping speed of the lye was controlled to keep the temperature of the system at 36℃±2℃, after about 3.5 h of dropping, the temperature was kept and the reaction was continued for 15 min, 500 kg of water was introduced to wash twice, and then the product was obtained by solid-liquid separation; wherein the mass ratio of 6-tert-butyl-3-methylphenol, dimethyl sulfate, lye and catalyst was 1:0.9:0.7:0.025.

[0061] Nitrification reaction

[0062] 2-1) The chilled water at 7-12℃ was introduced into the jacket of the nitrification reaction kettle to control the temperature in the nitrification reaction kettle to be below 12℃, and 210 kg of acetic anhydride (84%) was introduced into the reaction kettle under stirring;

[0063] 2-2) The remaining 40 kg of acetic anhydride was mixed with 135 kg of 3-methoxy-4-tert-butyltoluene to obtain a second mixture;

[0064] 2-3) The amount of chilled water introduced was controlled so that the temperature of the nitrification reaction kettle was reduced to below -2℃, and then 50 kg of nitric acid was added dropwise into the reaction kettle at a first speed of 7 g / min;

[0065] 2-4) The remaining 60 kg of nitric acid was added dropwise into the reaction kettle at a second speed of 3 g / min, and the second mixture was added dropwise into the reaction kettle at a third speed, and the temperature in the reaction kettle was controlled to be -6℃ to -4℃ to perform the nitrification reaction;

[0066] 2-5) The reaction product was transferred to a hydrolysis kettle (the temperature in the kettle was 0℃), and the product obtained in step 2-4) was mixed with water under stirring to wash until the product was yellow or light yellow.

[0067] Wherein the mass ratio of 3-methoxy-4-tert-butyltoluene, acetic anhydride and nitric acid was 1:1.85:0.81. The yield of this example was 98.6% and the purity of musk ambrette was 86.7% by gas chromatography test. Example

[0068] The musk ambrette prepared in Example 1 was refined.

[0069] S1, mix 300 kg of musk ambrette crude product, 2000 kg of 120# solvent oil, 20 kg of 30% lye, and 500 kg of water in an extraction kettle, heat to 75°C, stir for 15 min, then stand for 20 min, and discharge the alkali solution; pass 500 kg of water into the extraction kettle, heat to 75°C, stir for 15 min, then stand for 20 min, and discharge the alkali solution;

[0070] S2, under stirring, cool the extraction kettle so that the temperature of the material falls to below 45°C, filter the material to obtain a solid-phase product and a filtrate, and transfer the solid-phase product to a solid waste area;

[0071] S3, heat the filtrate obtained in step S2, and volatilize the solvent oil from the extraction kettle, return it to step S1 after condensation;

[0072] S4, transfer the product obtained in step S3 to a first crystallization kettle, mix it with 1000 kg of ethanol (the amount of ethanol is 3.3 times the amount of musk ambrette crude product), heat to 75°C, maintain the temperature for 15 min, then cool to 45°C, maintain the temperature for 15 min, then cool to 20°C, and obtain a primary crystallization product, and centrifuge the primary crystallization product to remove ethanol;

[0073] S5, transfer the product obtained in step S4 to a second crystallization kettle, mix it with 1000 kg of ethanol (the amount of ethanol is 3.3 times the amount of musk ambrette crude product), heat to 75°C, maintain the temperature for 15 min, then cool to 45°C, maintain the temperature for 15 min, then cool to 20°C, and obtain a primary crystallization product, and centrifuge the primary crystallization product to remove ethanol;

[0074] S6, dry the centrifuged product to obtain refined musk ambrette. Gas chromatography shows that the purity of the musk ambrette is 97.8%. Example

[0075] Prepare musk ambrette according to the method of Example 1, except that:

[0076] Nitration reaction:

[0077] 2-1) The amount of acetic anhydride is 230 kg;

[0078] 2-2) Mix 23 kg of acetic anhydride with 135 kg of 3-methoxy-4-tert-butyltoluene;

[0079] 2-3) Add 48.6 kg of nitric acid to the reaction kettle at a first speed of 9 g / min;

[0080] 2-4) 72.9 kg of nitric acid was added to the reaction kettle at a second speed of 4 g / min. The mass ratio of 3-methoxy-4-tert-butyltoluene, acetic anhydride and nitric acid was 1:1.9:0.9. The yield of this example was 97.1% and the purity of musk ambrette was 85.7% by gas chromatography.

[0081] The above musk ambrette was refined according to the refining method of Example 2. After refining, the purity of musk ambrette was 98.1%. Example

[0082] Musk ambrette was prepared according to the method of Example 1, except that:

[0083] Nitrification reaction:

[0084] 2-1) The amount of acetic anhydride was 181 kg;

[0085] 2-2) 35 kg of acetic anhydride was mixed with 135 kg of 3-methoxy-4-tert-butyltoluene;

[0086] 2-3) 60.75 kg of nitric acid was added to the reaction kettle at a first speed of 4 g / min;

[0087] 2-4) 74.25 kg of nitric acid was added to the reaction kettle at a second speed of 4 g / min. The mass ratio of 3-methoxy-4-tert-butyltoluene, acetic anhydride and nitric acid was 1:1.6:1. The yield of this example was 93.5% and the purity of musk ambrette was 80.2% by gas chromatography.

[0088] The above musk ambrette was refined according to the refining method of Example 2. After refining, the purity of musk ambrette was 91.3%. Example

[0089] Musk ambrette prepared in Example 1 was refined, except that:

[0090] In step S1, the amount of lye added was 24 kg;

[0091] In step S4, the product obtained in step S3 was transferred to the first crystallization kettle and mixed with 600 kg of ethanol (the amount of ethanol was twice the amount of musk ambrette crude product), heated to 80°C, and kept for 20 min. After cooling to 40°C, it was kept for 20 min. Then, it was cooled to 22°C, and the first crystallization product was obtained. The ethanol was removed by centrifugation.

[0092] S5, the product obtained in step S4 is transferred to a second crystallization kettle, mixed with 1200 kg of ethanol (the amount of ethanol is 4 times the amount of crude guixi musk), heated to 70 DEG C, and kept for 10 min, then cooled to 47 DEG C, and kept for 10 min, then cooled to 18 DEG C, to the first crystallization product, the first crystallization product is centrifuged, and the ethanol is removed;

[0093] S6, the product after centrifugation is dried to obtain refined guixi musk, which is tested by gas chromatography, and the purity of guixi musk is 98.3. Example

[0094] The refined guixi musk prepared in example 1 is refined, except that:

[0095] In step S1, the amount of lye added is 30 kg;

[0096] In step S4, the product obtained in step S3 is transferred to a first crystallization kettle, mixed with 1000 kg of ethanol (the amount of ethanol is 3 times the amount of crude guixi musk), heated to 78 DEG C, and kept for 15 min, then cooled to 45 DEG C, and kept for 15 min, to the first crystallization product, the first crystallization product is centrifuged, and the ethanol is removed;

[0097] S5, the product obtained in step S4 is transferred to a second crystallization kettle, mixed with 1200 kg of ethanol (the amount of ethanol is 4 times the amount of crude guixi musk), heated to 70 DEG C, and kept for 10 min, then cooled to 47 DEG C, and kept for 10 min, then cooled to 18 DEG C, to the first crystallization product, the first crystallization product is centrifuged, and the ethanol is removed;

[0098] S6, the product after centrifugation is dried to obtain refined guixi musk, which is tested by gas chromatography, and the purity of guixi musk is 98.3.

[0099] Comparative example 1

[0100] The guixi musk prepared according to the method of example 1 is refined, except that:

[0101] Nitration reaction:

[0102] 405 kg of concentrated sulfuric acid (98%) is dissolved in 810 kg of fuming nitric acid (95%), and is introduced into the nitric acid reaction kettle, and the temperature of the reaction kettle is controlled to below -2 DEG C, 135 kg of 3-methoxy-4-tert-butyl toluene is added dropwise into the reaction kettle, and the temperature in the reaction kettle is controlled at -6 DEG C to -4 DEG C, and the nitration reaction is carried out. During the reaction, a large amount of acid gas is generated, which causes serious corrosion to the reaction kettle, and guixi musk is obtained, which is tested by gas chromatography, and the yield of the comparative example is 91.2%, and the purity of guixi musk is 78.9%.

[0103] Comparative example 2

[0104] The sun musk prepared in Example 1 was refined, except that:

[0105] In step S1, 30% of the lye was not added.

[0106] The purity of the sun musk was 89.5% as measured by gas chromatography.

Claims

1. A process for the preparation of musk ambrette, characterized in that, The method comprises the following steps: 1) methylation reaction: 6-tert-butyl-3-methylphenol, dimethyl sulfate and lye are mixed in the presence of a catalyst to perform a methylation reaction, and then solid-liquid separation is performed to obtain 3-methoxy-4-tert-butyltoluene; 2) nitration reaction: the nitration reaction comprises the following steps: 2-1) under low-temperature conditions, 80-90 wt% of acetic anhydride is introduced into a reaction kettle under stirring conditions; 2-2) the remaining acetic anhydride is mixed with 3-methoxy-4-tert-butyltoluene to obtain a second mixture; 2-3) after the temperature is reduced to below -2°C, 40-50 wt% of nitric acid is added to the reaction kettle at a first speed; 2-4) while the remaining nitric acid is added to the reaction kettle at a second speed, the second mixture is added to the reaction kettle at a third speed to perform a nitration reaction; wherein the second speed is less than the first speed; the first speed is 5-7 g / min, and the second speed is 1-3 g / min; In step 2), the mass ratio of the 3-methoxy-4-tert-butyltoluene, the acetic anhydride and the nitric acid is 1:1.7-1.85:0.7-0.

81.

2. The production method according to claim 1, wherein In step 1), the catalyst is tetrabutylammonium bromide and / or tetrabutylammonium chloride.

3. The production method according to claim 2, wherein, The mass ratio of the 6-tert-butyl-3-methylphenol, the dimethyl sulfate, the lye and the catalyst is 1:0.8-1.5:0.8-1.5:0.01-0.

04.

4. The production method according to claim 2, wherein The methylation reaction comprises the following steps: 1-1) 6-tert-butyl-3-methylphenol, a catalyst and dimethyl sulfate are mixed at a first temperature to obtain a first mixture; 1-2) after the lye is added to the first mixture, a methylation reaction is performed, and then solid-liquid separation is performed to obtain 3-methoxy-4-tert-butyltoluene.

5. The production method according to claim 4, wherein In step 1-1), the first temperature is -10°C to -15°C; In step 1-2), the dropping speed of the lye is controlled so that the temperature of the system is 35-38°C, and the dropping time is 3-5 h; the time of the methylation reaction is 10-30 min.

6. The production method according to claim 2, wherein The second speed and the third speed make the temperature be -8°C to -2°C.

7. The method of any one of claims 1-6, wherein, The method further comprises the following refining steps: S1, under first stirring conditions, sun musk, solvent oil, alkali and water are mixed, then water washing is performed, and then the alkali solution is removed; wherein the mass ratio of the sun musk, the solvent oil, the alkali and the water is 1:4-8:0.05-0.08:1.4-2; the sun musk is prepared by the preparation method in any one of claims 1-6; S2, under second stirring conditions, the product of step S1 is subjected to cooling treatment, and then filtration is performed to obtain a solid-phase product and a filtrate; S3, the filtrate obtained in step S2 is heated to remove the solvent oil; S4, mixing the product obtained in step S3 with first ethanol, and performing primary crystallization to obtain a primary crystallization product; the primary crystallization comprises: heating the mixture of the product obtained in step S3 and first ethanol to 70-80°C, maintaining for 10-20 min, cooling to 40-48°C, and then cooling to 18-28°C; S5, mixing the primary crystallization product obtained in step S4 with second ethanol, and performing secondary crystallization to obtain a secondary crystallization product; the secondary crystallization comprises: heating the mixture of the product obtained in step S4 and second ethanol to 70-80°C, maintaining for 10-20 min, cooling to 40-48°C, and then cooling to 18-28°C; S6, drying the secondary crystallization product to obtain refined musk.

8. The production method according to claim 7, characterized by, In step S1, the water washing comprises: stirring at 75-80°C for 10-20 min, and then standing for 10-30 min; The water washing is performed at least twice; The solvent oil is 120# solvent oil.

9. The production method according to claim 8, characterized by, In step S2, the temperature is reduced to 45°C or lower; The solvent oil obtained in step S3 is returned to step S1.

10. The preparation method according to claim 8, characterized in that, The amount of the first ethanol and the second ethanol is independently 2-4 times of the refined musk.

11. The preparation method according to claim 8, characterized in that, The refining step further comprises: centrifuging the product after the primary crystallization and the secondary crystallization, respectively, to remove the first ethanol or the second ethanol.

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