Method for recovering ethyl acetate and application thereof

Abstract

The application relates to the technical field of ethyl acetate recovery, and discloses a recovery method of ethyl acetate and application thereof. The method is as follows: an acidic aqueous solution is added to concentrated ethyl acetate generated in the process of extracting hydrochloric atenolol with ethyl acetate as an organic solvent to adjust the pH value, the mixture is fully stirred and then is left to separate into layers to obtain organic phase one; purified water is used to wash the organic phase one, the mixture is fully stirred and then is left to separate into layers to obtain organic phase two; the organic phase two is concentrated to collect a fraction to obtain recovered ethyl acetate; and the application is as follows: the recovered ethyl acetate is applied to the extraction process of hydrochloric atenolol; the extraction effect of the recovered ethyl acetate can reach that of new ethyl acetate, so that the reutilization rate of ethyl acetate as an organic solvent can be improved, ethyl acetate material waste can be reduced, waste liquid treatment cost can be reduced, and environmental pollution can be reduced.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of ethyl acetate recovery, in particular, to a recovery method of ethyl acetate and application thereof. BACKGROUND

[0002] The molecular formula of articaine hydrochloride is C 13 H20N2O3S·HCl, the molecular weight is 320.8, and the structural formula is as follows:

[0003]

[0004] Articaine hydrochloride belongs to an amide local injection anesthetic, can block the nerve conduction along the nerve fibers of the injection site, has a local anesthetic effect, and has the following main characteristics compared with other local anesthetics: fast anesthetic onset time; strong tissue infiltration, no need for block anesthesia; high anesthetic efficacy, large safety range, appropriate anesthetic duration; low incidence of allergy, small influence on the cardiovascular system, and low toxic and side effects. Articaine hydrochloride is particularly suitable for surgical procedures involving osteotomy and mucosal incision. At present, it is the only oral cavity special local anesthetic supplied on the domestic market.

[0005] At present, the preparation method of articaine hydrochloride mainly includes a series of acylation, amination, salt formation, refining, beating and drying operations, and finally generates 4-methyl-3-[[1-oxo-2-(propylamino)-propyl]amino]-2-thiophene carboxylic acid methyl ester hydrochloride, that is, articaine hydrochloride. In the preparation method, a large amount of ethyl acetate is generated in the concentration process of the ethyl acetate phase after the extraction of the amination product 4-methyl-3-[[1-oxo-2-(propylamino)-propyl]amino]-2-thiophene carboxylic acid methyl ester after the amination reaction, but because an excessive amount of n-propylamine is added in the preparation process of 4-methyl-3-[[1-oxo-2-(propylamino)-propyl]amino]-2-thiophene carboxylic acid methyl ester, and the n-propylamine is easily dissolved in ethyl acetate, the obtained ethyl acetate in the concentration process contains n-propylamine, and cannot be directly reused, but only can be directly discarded as waste solvent, and a large amount of ethyl acetate is needed for the extraction of 4-methyl-3-[[1-oxo-2-(propylamino)-propyl]amino]-2-thiophene carboxylic acid methyl ester generated in the amination reaction, so directly treating the waste liquid will cause great waste.

[0006] Therefore, the treatment of the ethyl acetate generated in the concentration process and the reuse of the ethyl acetate for the extraction of 4-methyl-3-[[1-oxo-2-(propylamino)-propyl]amino]-2-thiophene carboxylic acid methyl ester generated in the amination are of great significance to the preparation process and environmental protection of articaine hydrochloride. SUMMARY

[0007] The application provides a recovery method of ethyl acetate and application thereof, and solves the problem of serious waste of ethyl acetate in the related art.

[0008] The technical scheme of the application is as follows:

[0009] In a first aspect, the application discloses a recovery method of ethyl acetate, comprising the following steps:

[0010] S1: adding an acidic aqueous solution to concentrated ethyl acetate generated in the process of extracting hydrochloric acid atropine with ethyl acetate as an organic solvent for pH adjustment, fully stirring and then layering after standing to obtain organic phase one;

[0011] S2: washing the organic phase one with purified water, fully stirring and then layering after standing to obtain organic phase two; and performing concentration treatment on the organic phase two to collect a fraction to obtain recovered ethyl acetate.

[0012] Further, in step S1, the acidic aqueous solution comprises a combination of one or more of hydrochloric acid, phosphoric acid, acetic acid and sulfuric acid;

[0013] Preferably, the acidic aqueous solution is hydrochloric acid.

[0014] Further, the concentration of the acidic aqueous solution is 0.1 mol / L-1 mol / L;

[0015] Preferably, the concentration of the acidic aqueous solution is 0.1 mol / L.

[0016] Further, in step S1, when the acidic aqueous solution is added for pH adjustment, the pH value is adjusted to 1-6;

[0017] Preferably, the pH value is adjusted to 4-5.

[0018] Further, in step S2, when the organic phase one is washed with purified water, the amount of purified water is 5%-30% of the amount of concentrated ethyl acetate;

[0019] Preferably, the amount of purified water is 10% of the amount of concentrated ethyl acetate.

[0020] Further, in step S2, the concentration treatment method is a reduced-pressure vacuum concentration method, the vacuum degree is-(0.04-0.10) MPa, and the collection temperature is 30-70 DEG C.

[0021] Preferably, the vacuum degree is-(0.08-0.10) MPa, and the collection temperature is 40-50 DEG C.

[0022] Further, the collection temperature is the temperature of the organic phase two during the reduced-pressure vacuum concentration, which is convenient for observing the temperature change in the production process.

[0023] Further, in steps S1 and S2, the stirring time is 5 min-60 min, and the standing time is 5 min-60 min.

[0024] Preferably, the stirring time is 10 min-15 min, and the standing time is 20 min-30 min.

[0025] Based on this, a preferred method for recovering ethyl acetate in the present application is obtained, which is specifically as follows:

[0026] Step one: in the process of extracting hydrochloric acid atropine with ethyl acetate as an organic solvent, a concentrated hydrochloric acid solution with a concentration of 0.1 mol / L is added to the concentrated ethyl acetate, the pH is adjusted to 4, and after 10 min of sufficient stirring, 25 min of standing and layering, organic phase one is obtained;

[0027] Step two: sufficient purified water is used to wash the organic phase one, 10 min of sufficient stirring is performed, 25 min of standing and layering is performed, and organic phase two is obtained; the organic phase two is subjected to concentrated treatment by using a reduced pressure vacuum concentration method (vacuum degree-0.08 MPa, collection temperature 45°C), the fraction is collected, and the recovered ethyl acetate is obtained.

[0028] In a second aspect, the present application also discloses an application of the method for recovering ethyl acetate as described above, which applies the recovered ethyl acetate to the extraction process of hydrochloric acid atropine, can improve the reutilization rate of ethyl acetate as an organic solvent, reduce the waste of ethyl acetate material, reduce the waste liquid treatment cost, and reduce environmental pollution.

[0029] Further, the steps of applying the recovered ethyl acetate to the extraction process of hydrochloric acid atropine are as follows:

[0030] Step one: 4-methyl-3[[1-oxo-2-(chloro)-propyl]amino]-2-thiophene carboxylic acid methyl ester is dissolved in DMF (dimethylformamide), the temperature is raised to 35°C±2°C for dissolution, n-propylamine is started to be added dropwise, the temperature is controlled at 35°C±2°C, after the dropwise addition is completed, the temperature is controlled at 35-40°C, and the reaction is kept for 24 h; after the reaction is completed, the recovered ethyl acetate and the prepared saturated sodium carbonate aqueous solution are added to the liquid, 20 min of stirring is performed, 30 min of standing is performed, layering is performed, and the organic phase and the aqueous phase are collected separately;

[0031] Step two: the recovered ethyl acetate is added to the collected aqueous phase again, 20 min of stirring is performed, 30 min of standing is performed, layering is performed, this step is repeated once again, the aqueous phase is collected, and the organic phases are combined; anhydrous sodium sulfate is added to the collected combined organic phase, drying is performed, and then concentration is performed, the organic phase is distilled off, and an oily substance is obtained.

[0032] Step three: add 1.3 times amount of acetone to the oil, stir to dissolve, control the temperature ≤40℃, use concentrated hydrochloric acid to adjust the pH to 5-6, after adjustment, cool to 0-5℃, and keep for 24h, filter, and wash the filter cake with a small amount of acetone; add 2 times amount of acetone to the obtained solid, heat to reflux and dissolve, keep for 15min, filter, cool the filtrate to 0-5℃, keep for 24h, filter, wash the filter cake with a small amount of acetone, repeat the operation once again, and vacuum dry the obtained solid to obtain the articaine hydrochloride.

[0033] The beneficial effects of the present application are:

[0034] The present application recycles the concentrated ethyl acetate generated in the process of extracting articaine hydrochloride with ethyl acetate as an organic solvent, obtains recycled ethyl acetate with high standard of recovery rate and purity, and continues to apply the recycled ethyl acetate to the extraction process of articaine hydrochloride, so that the extraction effect can reach that of new ethyl acetate, thereby improving the reutilization rate of ethyl acetate as an organic solvent, reducing the waste of ethyl acetate materials, reducing the cost of waste liquid treatment, and reducing environmental pollution. DETAILED DESCRIPTION

[0035] The technical solutions in the embodiments of the present application will be described clearly and completely below. Obviously, the described embodiments are only part of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor also fall within the scope of protection of the present application.

[0036] In the following examples, the experimental methods are conventional methods, and are carried out according to the techniques or conditions described in the literature in the art or according to the product instructions, unless otherwise specified. The materials, reagents, etc. used in the following examples can be obtained from commercial channels, unless otherwise specified.

[0037] Example 1

[0038] Preparation of recycled ethyl acetate.

[0039] Step one: add a hydrochloric acid solution with a concentration of 0.1 mol / L to 1 kg of concentrated ethyl acetate generated in the process of extracting articaine hydrochloride with ethyl acetate as an organic solvent, adjust the pH to 4, stir for 10min, and then stand for 25min to separate the layers, to obtain organic phase one;

[0040] Step two: wash the organic phase one with 100g of purified water, stir for 10min, stand for 25min to separate the layers, to obtain organic phase two; and use a reduced pressure vacuum concentration method (vacuum degree-0.08MPa, collection temperature 45℃) to concentrate the organic phase two, collect the fraction, and obtain the recycled ethyl acetate.

[0041] The mass of the recovered ethyl acetate was 850 g, the recovery rate of the ethyl acetate was 85%, and the purity of the ethyl acetate was 99.9% (the standard content is ≥ 99.5%).

[0042] Example 2

[0043] The recovered ethyl acetate was prepared.

[0044] The preparation process was the same as that of Example 1, except that in step one, 0.1 mol / L of a hydrochloric acid solution was replaced by 0.1 mol / L of a phosphoric acid aqueous solution, and other conditions were completely the same. Finally, the recovered ethyl acetate was obtained.

[0045] The mass of the recovered ethyl acetate was 849 g, the recovery rate of the ethyl acetate was 84.9%, and the purity of the ethyl acetate was 99.6%.

[0046] Example 3

[0047] The recovered ethyl acetate was prepared.

[0048] The preparation process was the same as that of Example 1, except that in step one, 0.1 mol / L of a hydrochloric acid solution was replaced by 0.1 mol / L of an acetic acid aqueous solution, and other conditions were completely the same. Finally, the recovered ethyl acetate was obtained.

[0049] The mass of the recovered ethyl acetate was 851 g, the recovery rate of the ethyl acetate was 85.1%, and the purity of the ethyl acetate was 99.5%.

[0050] Example 4

[0051] The recovered ethyl acetate was prepared.

[0052] The preparation process was the same as that of Example 1, except that in step one, 0.1 mol / L of a hydrochloric acid solution was replaced by 0.1 mol / L of a sulfuric acid aqueous solution, and other conditions were completely the same. Finally, the recovered ethyl acetate was obtained.

[0053] The mass of the recovered ethyl acetate was 850 g, the recovery rate of the ethyl acetate was 85%, and the purity of the ethyl acetate was 99.6%.

[0054] The recovery rate and purity of the recovered ethyl acetate prepared in Examples 1-4 are listed in Table 1, and Table 1 is as follows:

[0055] Table 1

[0056] Recovery rate (%) Purity (%) (standard ≥99.5%) Example 1 85.0 99.9 Example 2 84.9 99.6 Example 3 85.1 99.5 Example 4 85.0 99.6

[0057] The data in Table 1 are analyzed, and it can be known that the recovery rate of the recovered ethyl acetate reaches about 85% when the concentrated ethyl acetate generated in the process of extracting articaine hydrochloride with ethyl acetate as an organic solvent is recovered by the recovery method of the application, the recovery rate is relatively high, the purity reaches 99.5% or above, and the purity meets the standard purity, so the recovered ethyl acetate can be reused.

[0058] Test Example 1-4

[0059] Articaine hydrochloride is extracted with ethyl acetate as an organic solvent.

[0060] The recovered ethyl acetate in Examples 1-4 is respectively applied to the extraction process of articaine hydrochloride to perform four groups of tests, and the test extraction process of each group is as follows.

[0061] Step one: 100 g of 4-methyl-3[[1-oxo-2-(chloro)-propyl]amino]-2-thiophene carboxylic acid methyl ester is dissolved in 300 g of DMF, the temperature is raised to 35°C for dissolution, 100 mL of n-propylamine is added dropwise, the temperature is controlled at 35°C, after the dropwise addition is completed, the temperature is controlled at 35°C, and the reaction is kept for 24 h; after the reaction is completed, 100 g of recovered ethyl acetate and 100 g of prepared saturated aqueous sodium carbonate solution are added to the liquid, stirred for 20 min, and separated into organic phase and aqueous phase after standing for 30 min;

[0062] Step two: 200 g of recovered ethyl acetate is added to the collected aqueous phase, stirred for 20 min, and separated into layers after standing for 30 min, and this step is repeated once, the aqueous phase is collected, and the organic phases are combined; 10 g of anhydrous sodium sulfate is added to the collected combined organic phase, dried, and then concentrated, and the organic phase is distilled off to obtain an oil;

[0063] Step three: 1.3 times of acetone is added to the oil, stirred and dissolved, the temperature is controlled to be ≤40°C, concentrated hydrochloric acid is used to adjust the pH to 5, after the adjustment is completed, the temperature is lowered to 3°C, and the crystallization is kept for 24 h, then filtered, the filter cake is washed with 1 times of acetone, the obtained solid after washing is added with 2 times of acetone, heated to reflux and dissolved, and then kept at 25°C for 15 min, filtered, the filtrate is lowered to 3°C, and the crystallization is kept for 24 h, then filtered, the filter cake is washed with 1 times of acetone, and this operation is repeated once, the obtained solid is vacuum dried at 70°C for 8 h, and finally articaine hydrochloride is obtained.

[0064] Comparative Example 1

[0065] Articaine hydrochloride is extracted with ethyl acetate as an organic solvent.

[0066] Compared with the test example, the only difference is that the recovered ethyl acetate is replaced by new ethyl acetate (ethyl acetate purchased and used for the first time, the purity is 99.8%), and other conditions are completely the same, and finally articaine hydrochloride is obtained.

[0067] The yield and purity of the extracted articaine hydrochloride in Test Example 1-4 and Comparative Example 1 were calculated and detected, and the results are listed in Table 2 as follows:

[0068] Table 2

[0069]

[0070]

[0071] According to the analysis of the data in Table 2, it can be seen that the yield and purity of the extracted articaine hydrochloride in Test Example 1-4 are not much different from those of the extracted articaine hydrochloride in Comparative Example 1, and both of them meet the use requirements; this shows that the recovered ethyl acetate prepared by using the recovery method of the present application applied to the extraction process of articaine hydrochloride can achieve a better extraction effect.

[0072] The above is only a preferred embodiment of the present application, and is not used to limit the present application, and 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. An application of a method for recovering ethyl acetate, characterized in that, The steps include: S1: adding an acidic aqueous solution to concentrated ethyl acetate produced in the process of extracting articaine hydrochloride with ethyl acetate as an organic solvent to adjust the pH, stirring thoroughly and then standing for stratification to obtain an organic phase 1, wherein the concentrated ethyl acetate contains n-propylamine; S2: washing the organic phase 1 with purified water, stirring thoroughly, and then standing to separate the layers to obtain an organic phase 2; concentrating the organic phase 2, collecting the fractions, and obtaining recovered ethyl acetate; In step S1, the acidic aqueous solution includes a combination of one or more of hydrochloric acid, phosphoric acid, acetic acid and sulfuric acid; The concentration of the acidic aqueous solution is 0.1 mol / L; In step S1, when an acidic aqueous solution is added for pH adjustment, the pH value is adjusted to 4-5; In step S2, the concentration treatment method is: using a reduced pressure vacuum concentration method, a vacuum degree of -(0.08-0.10) MPa, and a collection temperature of 40°C-50°C; The recovered ethyl acetate is used in the extraction process of articaine hydrochloride.

2. The application of the method for recovering ethyl acetate according to claim 1, wherein In step S2, when the organic phase 1 is washed with purified water, the amount of purified water used is 5%-30% of the amount of concentrated ethyl acetate used.

3. The application of the method for recovering ethyl acetate according to claim 1, wherein The collection temperature is the feed liquid temperature of the organic phase 2 during reduced pressure vacuum concentration.

4. The application of the method for recovering ethyl acetate according to claim 1, wherein In steps S1 and S2, the stirring time is 5 min to 60 min, and the standing time is 5 min to 60 min.

Images