Method for purifying methyl isobutyrylacetate

Abstract

The invention discloses a method for purifying methyl isobutyrylacetate, which comprises the following steps of: introducing a concentrated material obtained at the front end into the middle part of a continuous rectifying tower T1 for rectifying to obtain light components at the top of the tower, and removing dichloromethane, methanol and 3-methyl-2-butanone; a tower kettle substrate of the continuous rectifying tower T1 enters the middle part of a continuous rectifying tower T2 to be rectified, and diethyl methyl ester with the purity of 90% is obtained at the tower top; a tower kettle substrate of the continuous rectifying tower T2 enters the middle part of a continuous rectifying tower T3 to be rectified, and an isobutyryl methyl acetate product is produced at the tower top; the method has the advantages that the methyl isobutyrylacetate is purified by adopting a continuous rectification method, and rectification parameters are optimized, so that the yield of the methyl isobutyrylacetate can reach 85% or above under the condition that the purity of the methyl isobutyrylacetate is not lower than 99%; and the continuous rectification is continuous feeding and continuous extraction, the retention time is short, and the energy consumption is low.

Description

TECHNICAL FIELD

[0001] The present application relates to the chemical technology field, specifically to a purification method of methyl isobutyryl acetate. BACKGROUND

[0002] In the treatment of cardiovascular and cerebrovascular diseases, atorvastatin is the most effective statin lipid-regulating drug, which has the largest effect of reducing low-density lipoprotein (LDL-C) and the strongest effect of reducing triglycerides, and can increase the level of high-density lipoprotein cholesterol (HDI-C). It is the only statin drug that has been proven to be superior to vascular reconstruction in reducing cardiovascular events. Methyl isobutyryl acetate is a key intermediate for the synthesis of atorvastatin, which is irreplaceable.

[0003] At present, the synthesis of methyl isobutyryl acetate (M1) is mainly by reacting methyl acetoacetate with isobutyryl chloride to synthesize a mixed solution containing methyl isobutyryl acetate, and the final methyl isobutyryl acetate product is obtained by purification.

[0004] At present, the purification process is basically divided into layering, washing, water washing, normal pressure concentration and rectification; the rectification is completed twice, after rectification by the first batch rectification tower, the qualified M1 yield is about 30%~40%, the remaining high concentration M1 crude material is collected and fed into the second batch rectification tower for rectification, and the qualified M1 product is obtained, the total yield of M1 after two times of rectification is about 75%, and the purity is more than 99%. The existing rectification method has the following problems: the batch rectification operation has the characteristics of large reflux ratio and high vacuum operation, the operation time is long, and the energy consumption is high; since methyl isobutyryl acetate is a heat-sensitive material, it is easy to deteriorate to generate methanol and 3-methyl-2-butanone, at the same time, the boiling points of the product methyl isobutyryl acetate and methyl acetoacetate are similar, which leads to difficult separation of the product and low yield. Therefore, in a short period of time, obtaining high-purity, high-yield and low-energy consumption methyl isobutyryl acetate is a problem to be solved at present. SUMMARY

[0005] The purpose of the present application is to provide a purification method of methyl isobutyryl acetate with high purity, high yield and low energy consumption, to solve the problems raised in the background art.

[0006] The present application is implemented by the following technical solutions:

[0007] A purification method of methyl isobutyryl acetate, comprising the following steps:

[0008] (1) The concentrated material obtained in the front end is introduced into the middle part of the continuous rectification tower T1 for rectification, the light components on the top of the tower are removed, and dichloromethane, methanol and 3-methyl-2-butanone are removed;

[0009] (2) The bottom material of continuous rectification tower T1 enters the middle part of continuous rectification tower T2 for rectification, and the top is dimethyl butyral 90% in purity;

[0010] (3) The bottom material of continuous rectification tower T2 enters the middle part of continuous rectification tower T3 for rectification, and the top is methyl isobutyryl acetate product.

[0011] Preferably, the top temperature of continuous rectification tower T1 is 35-65℃, the bottom temperature is 85-100℃, the reflux ratio is 100-300, and the pressure is negative pressure 0.1.

[0012] Preferably, the top temperature of continuous rectification tower T2 is 35-65℃, the bottom temperature is 85-100℃, the reflux ratio is 100-300, and the pressure is negative pressure 0.1.

[0013] Preferably, the top temperature of continuous rectification tower T3 is 35-65℃, the bottom temperature is less than 85-100℃, the reflux ratio is 100-300, and the pressure is negative pressure 0.1.

[0014] Advantages of the present application:

[0015] The present application purifies methyl isobutyryl acetate by using continuous rectification method, optimizes rectification parameters, so that the yield of methyl isobutyryl acetate can reach more than 85% under the condition of ensuring the purity of not less than 99%; and continuous rectification is continuous feeding, continuous production, short residence time and low energy consumption. BRIEF DESCRIPTION OF DRAWINGS

[0016] Figure 1 It is a flow chart of the purification method of methyl isobutyryl acetate in example 1;

[0017] Figure 2 It is a structure diagram of continuous rectification; DETAILED DESCRIPTION

[0018] The technical solutions in the embodiments of the present application will be clearly and completely described below with reference to the drawings in the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, not all. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor are within the scope of protection of the present application.

[0019] Example 1: please refer to Figure 1 A purification method of methyl isobutyryl acetate, comprising the following steps:

[0020] S1 feeding and stirring:

[0021] First, add 4800 kg of dichloromethane (liquid, solvent, melting point -97°C, boiling point 39.7°C, insoluble in water) to the dry reaction kettle through the high metering tank, start stirring, maintain a slight negative pressure in the reaction kettle, slowly add 420 kg of calcium hydroxide (solid, powder, pneumatic conveying, no dust) through the pipe, stir for 30 min, then open the circulating water jacket, control the reaction kettle temperature at 25-30°C, start dropping 600 kg of methyl acetoacetate (liquid, melting point -28°C, boiling point 169-170°C, easily soluble in water), the dropping time is 1.5 h, and after 1 h of incubation, drop 600 kg of isobutyryl chloride (melting point -90°C, boiling point 90.9°C, easily decomposed by water), control the dropping time at about 2 h.

[0022] The main pollutant of this process is the waste gas G1-6 generated by feeding. The main component of the feeding waste gas is dichloromethane, and the content of isobutyryl chloride and methyl acetoacetate is very low, which is below the effective numerical value and can be ignored.

[0023] S2 incubation reaction:

[0024] After the feeding and dropping are completed, open the steam jacket and start heating, control the reaction kettle temperature at 32-40°C, get a mixed solution of isobutyryl methyl acetoacetate and other by-products, which needs to be purified in subsequent process steps, and after 3.5 h of incubation, transfer to hydrolysis.

[0025] S3 hydrolysis:

[0026] Open the reaction kettle refrigerated brine jacket to 20°C, add 1350 kg of 27.27% ammonium chloride aqueous solution to the mixed solution at 20-30°C, adjust the pH in the reaction kettle to neutral to slightly acidic, add 67.5 kg of calcium hydroxide after the dropping is completed, adjust the pH to 8.5-9.5, if not, add 100 kg of 20% ammonia water, adjust for 3 h. After the incubation reaction is completed, transfer to acidification.

[0027] S4 acidification:

[0028] Cool to below 30°C, add 50 kg of 30% hydrochloric acid to the mixed solution, remove calcium hydroxide, generate weak electrolyte isobutyric acid and acetic acid, the reaction formula is as follows:

[0029] Ca(OH)2+2HCl→CaCl2+2H2O

[0030]

[0031] Ca(CH3COO)2+2HCl→2CH3COOH+CaCl2

[0032] Stir for 30 min after the pH is less than 1, and close the refrigerated brine jacket.

[0033] The main pollutants of this process are waste gas G1-7 generated by the volatilization of hydrochloric acid. The waste gas is treated by an alkali absorption device, and the treated alkali liquor is adjusted in pH and then sent to a sewage treatment station for treatment.

[0034] S5 first layering:

[0035] Add 3000 kg of water, stir for 10 min, and stand for layering. The water layer is sent to a distillation kettle for distillation treatment. After the distillation kettle is heated by hot steam, the water jacket is recovered by secondary condensation. The organic layer is sent to a washing kettle.

[0036] After the organic layer is divided into a washing kettle, 3000 kg of baking soda solution is added to remove excess acid. Stir for 30 min and layer. The water layer is distilled for treatment.

[0037] The washing water is concentrated in a washing water storage tank. The main substances in the washing water are hydrogen chloride, calcium chloride, and ammonium chloride, and contain a certain amount of organic impurities (dichloromethane, isobutyric acid, acetic acid, and methyl isobutyryl acetate). Calcium chloride and ammonium chloride are obtained by evaporation and fractional crystallization, and are reused after analysis.

[0038] Waste gas G1-8 is generated during the evaporation and crystallization process. The main components of the waste gas are dichloromethane and water vapor. Waste water W2 is generated by condensing and recovering water during the evaporation process, mainly water and organic matter. The kettle bottom residue S1-2 generated during the evaporation process is an organic matter, mainly methyl isobutyryl acetate, fluorobenzene, isobutyrate, and chloride.

[0039] S6 second layering:

[0040] After the organic layer is divided into a washing kettle, 80 kg of baking soda solution is added to remove excess hydrochloric acid and a small amount of organic acid in the organic layer. The reaction is as follows:

[0041]

[0042] CH3COOH + NaHCO3 → CH3COONa + H2O + CO2

[0043] HCl + NaHCO3 → NaCl + H2O + CO2

[0044] Stir for 30 min and layer. The water layer is distilled for treatment. The organic layer is washed with 1200 kg of water, and the washing water is distilled and purified for reuse after washing.

[0045] Waste gas G1-9 is generated during the distillation of the water layer, mainly water vapor and dichloromethane. Distillation produces residual liquid S1-3, and the distilled water is reused for washing. At the same time, a small amount of waste gas G1-10 is generated during the reaction process, mainly carbon dioxide. The waste gas is collected and treated by a tail gas collection device and then emptied.

[0046] S7 water washing:

[0047] The organic layer is washed with 2000 kg of water, and after washing, the layers are separated, the washing water is recycled, and the organic layer is sent to the concentration kettle.

[0048] The washing water is concentrated in the washing water pool, the main substances in the washing water are calcium chloride, sodium chloride, sodium bicarbonate and ammonium chloride, and a small amount of organic impurities, waste gas G1-11 is generated during the distillation and condensation process, the main components of the waste gas are dichloromethane and water vapor, evaporation, and the residue S1-4 generated at the bottom of the kettle is mainly sodium salts such as sodium chloride, sodium acetate, sodium isobutyrate and a small amount of dichloromethane, methyl isobutyryl acetate and methyl acetoacetate.

[0049] S8 atmospheric concentration:

[0050] The organic layer is pressed into the concentration kettle, the steam jacket is opened to warm up to 30-55℃, and the solvent dichloromethane (melting point -97℃, boiling point 39.75℃, density 1.325g / cm3) is evaporated, and the condensed dichloromethane is recovered, the collected dichloromethane is sent to the high tank for use, the concentration is carried out until the amount of dichloromethane evaporated is small, the temperature is gradually increased to 70℃ to end the solvent recovery, the hot steam jacket is closed, and the natural cooling is carried out to 45℃ to discharge, and the concentrated material enters the continuous distillation.

[0051] The waste gas G1-12 is generated during the atmospheric distillation concentration process, and the main components of the waste gas are dichloromethane and water vapor.

[0052] S9 continuous distillation:

[0053] (1) The concentrated material obtained at the front end is introduced into the middle of the continuous rectification tower T1 for rectification, the light components at the top are removed, and dichloromethane, methanol and 3-methyl-2-butanone are removed; the top temperature of the continuous rectification tower T1 is 65℃, the bottom temperature is 100℃, the reflux ratio is 150, and the pressure is negative pressure 0.1.

[0054] (2) The bottom material of the continuous rectification tower T1 is introduced into the middle of the continuous rectification tower T2 for rectification, and the top is diethyl methyl ester with a purity of 90%; the top temperature of the continuous rectification tower T2 is 65℃, the bottom temperature is 100℃, the reflux ratio is 150, and the pressure is negative pressure 0.1.

[0055] (3) The bottom material of the continuous rectification tower T2 is introduced into the middle of the continuous rectification tower T3 for rectification, and the top produces methyl isobutyryl acetate product; the top temperature of the continuous rectification tower T3 is 60℃, the bottom temperature is 100℃, the reflux ratio is 150, and the pressure is negative pressure 0.1.

[0056] The purity of the methyl isobutyryl acetate product obtained by the method of this embodiment 1 is 99%, the yield is 85%, the energy consumption is 25%, and the time used is 80 hours.

[0057] Comparative Example 1: A purification method of methyl isobutyryl acetate, which is different from Example 1 in that the continuous distillation step S9 in Example 1 is replaced by a conventional batch rectification mode, and the remaining steps and parameters are exactly the same as those in Example 1.

[0058] The purity of the methyl isobutyryl acetate product obtained by the method of Comparative Example 1 is 99%, the yield is 75%, the energy consumption is 30%, and the time used is 96 hours.

[0059] Comparing Example 1 with Comparative Example 1, the purity of the methyl isobutyryl acetate product prepared is comparable, but the yield of the product of Example 1 is significantly higher than that of Comparative Example 1, and the energy consumption and the time used are significantly lower than those of Comparative Example 1.

[0060] The above only describes the preferred embodiments of the present application and is not intended to limit the present application. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present application shall be included in the protection scope of the present application.

Claims

1. A method for purifying methyl isobutyrylacetate, characterized in that, Includes the following steps: (1) The concentrated material obtained from the front end is fed into the middle of the continuous distillation column T1 for distillation. The top of the column is a light component, and dichloromethane, methanol and 3-methyl-2-butanone are removed. (2) The bottom product of continuous distillation column T1 enters the middle part of continuous distillation column T2 for distillation, and the top of the column is diethyl methyl ester with a purity of 90%. (3) The bottom product of continuous distillation column T2 enters the middle part of continuous distillation column T3 for distillation, and the top of the column produces methyl isobutyryl acetate.

2. The purification method for methyl isobutyrylacetate according to claim 1, characterized in that, The continuous distillation column T1 has a top temperature of 35℃-65℃, a bottom temperature of 85℃-100℃, a reflux ratio of 100-300, and a negative pressure of 0.

1.

3. The purification method for methyl isobutyrylacetate according to claim 1, characterized in that, The continuous distillation column T2 has a top temperature of 35℃-65℃, a bottom temperature of 85℃-100℃, a reflux ratio of 100-300, and a negative pressure of 0.

1.

4. The purification method for methyl isobutyrylacetate according to claim 1, characterized in that, The continuous distillation column T3 has a top temperature of 35℃-65℃, a bottom temperature of less than 85℃-100℃, a reflux ratio of 100-300, and a pressure of negative 0.1.

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