Recovery method and application of ethyl acetate

Abstract

The invention relates to the technical field of ethyl acetate recovery, and provides an ethyl acetate recovery method and application thereof.The method comprises the steps that an acidic aqueous solution is added into concentrated ethyl acetate generated in the process that ethyl acetate serves as an organic solvent to extract articaine hydrochloride for pH adjustment, standing layering is conducted after sufficient stirring, and an organic phase I is obtained; washing the organic phase I with purified water, fully stirring, and standing for layering to obtain an organic phase II; the second organic phase is concentrated, fractions are collected, and recycled ethyl acetate is obtained; according to the application, the recycled ethyl acetate is applied to the extraction process of articaine hydrochloride; the extraction effect of the recovered ethyl acetate can reach the extraction effect of new ethyl acetate, so that the reutilization rate of the ethyl acetate as an organic solvent can be improved, the waste of the ethyl acetate material is reduced, the waste liquid treatment cost is reduced, and the environmental pollution is reduced.

Description

Technical Field

[0001] The invention relates to the technical field of ethyl acetate recovery, and in particular to a method for recovering ethyl acetate and application thereof. Background Art

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

[0003]

[0004] Articaine hydrochloride is an amide local injection anesthetic that can block nerve conduction along the nerve fibers at the injection site and act as a local anesthetic. Compared with other local anesthetics, the main characteristics of articaine hydrochloride are fast onset of anesthesia: strong tissue infiltration, no need for block anesthesia; high anesthetic efficacy, large safety range, and appropriate duration of anesthesia; low incidence of allergies, small impact on the cardiovascular system, and low toxic side effects. It is particularly suitable for surgical procedures involving osteotomy and mucosal incision. At the same time, it is also the only oral local anesthetic currently available on the domestic market.

[0005] At present, the preparation method of articaine hydrochloride mainly includes a series of acylation, amination, salification, refining, pulping and drying operations, and finally produces 4-methyl-3-[[1-oxo-2-(propylamino)-propyl]amino]-2-thiophenecarboxylic acid methyl ester hydrochloride, that is, articaine hydrochloride. In the preparation method, a large amount of ethyl acetate is produced during the concentration process of the ethyl acetate phase after the amination product 4-methyl-3-[[1-oxo-2-(propylamino)-propyl]amino]-2-thiophenecarboxylic acid methyl ester is extracted after the amination reaction. However, since an excessive amount of n-propylamine is added during the preparation process of 4-methyl-3-[[1-oxo-2-(propylamino)-propyl]amino]-2-thiophenecarboxylic acid methyl ester, and n-propylamine is easily soluble in ethyl acetate, the ethyl acetate obtained by concentration contains n-propylamine and cannot be directly reused, but can only be directly discarded as a waste solvent. The 4-methyl-3-[[1-oxo-2-(propylamino)-propyl]amino]-2-thiophenecarboxylic acid methyl ester generated by the extraction amination reaction requires a large amount of ethyl acetate, so directly treating it as a waste liquid will cause huge waste.

[0006] Therefore, treating the ethyl acetate produced in the concentration process and reusing it for extracting the 4-methyl-3-[[1-oxo-2-(propylamino)-propyl]amino]-2-thiophenecarboxylic acid methyl ester produced by amination is of great significance to the preparation process of articaine hydrochloride and environmental protection. Summary of the invention

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

[0008] The technical solution of the present invention is as follows:

[0009] In a first aspect, the present invention discloses a method for recovering ethyl acetate, comprising the following steps:

[0010] S1: adding an acidic aqueous solution to the concentrated ethyl acetate produced in the process of extracting articaine hydrochloride with ethyl acetate as an organic solvent to adjust the pH, and standing and stratifying after sufficient stirring to obtain an organic phase 1;

[0011] S2: washing the organic phase 1 with purified water, stirring it fully and then standing it for stratification to obtain an organic phase 2; concentrating the organic phase 2, collecting the fractions, and obtaining recovered ethyl acetate.

[0012] Further, in step S1, the acidic aqueous solution includes 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 an 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] Furthermore, 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;

[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: using a reduced pressure vacuum concentration method, the vacuum degree is -(0.04-0.10)MPa, and the collection temperature is 30°C-70°C;

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

[0022] Furthermore, the collection temperature is the feed liquid temperature of the organic phase 2 during reduced pressure vacuum concentration, which is convenient for observing temperature changes during the production process.

[0023] Furthermore, in steps S1 and S2, the stirring time is 5 min to 60 min, and the standing time is 5 min to 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 invention is obtained, which is as follows:

[0026] Step 1: adding a 0.1 mol / L hydrochloric acid solution to concentrated ethyl acetate produced in the process of extracting articaine hydrochloride with ethyl acetate as an organic solvent, adjusting the pH to 4, stirring for 10 min, standing for 25 min, and stratifying to obtain an organic phase 1;

[0027] Step 2: Wash the organic phase 1 with sufficient purified water, stir it for 10 minutes, and then let it stand for 25 minutes to separate the layers to obtain an organic phase 2; concentrate the organic phase 2 using a reduced pressure vacuum concentration method (vacuum degree -0.08MPa, collection temperature 45°C), collect the fractions, and obtain recovered ethyl acetate.

[0028] In a second aspect, the present invention also discloses an application of the ethyl acetate recovery method as described above, and the recovered ethyl acetate is applied to the extraction process of articaine hydrochloride, which can improve the reuse rate of ethyl acetate as an organic solvent, reduce the waste of ethyl acetate materials, reduce the cost of waste liquid treatment, and reduce environmental pollution.

[0029] Further, the step of the extraction process of the ethyl acetate recovered being applied to articaine hydrochloride is as follows:

[0030] Step 1: dissolve 4-methyl-3[[1-oxo-2-(chloro)-propyl]amino]-2-thiophenecarboxylic acid methyl ester in DMF (dimethylformamide), heat to 35°C±2°C to dissolve, start to drop n-propylamine, control the temperature at 35°C±2°C, after the dropwise addition is completed, control the temperature at 35-40°C, and keep the temperature for reaction for 24 hours; after the reaction is completed, add the recovered ethyl acetate and the prepared saturated aqueous solution of sodium carbonate to the feed liquid, stir for 20 minutes, stand for 30 minutes to separate, and collect the organic phase and the aqueous phase separately;

[0031] Step 2: Add the recovered ethyl acetate to the collected aqueous phase again, stir for 20 minutes, let stand for 30 minutes to separate the layers, repeat this step once, collect the aqueous phase, and combine the organic phases; then add anhydrous sodium sulfate to the collected combined organic phases, dry them, and concentrate them, and evaporate the organic phase to obtain an oily substance;

[0032] Step 3: Add 1.3 times the amount of acetone to the oily substance, stir and dissolve, control the temperature ≤40°C, use concentrated hydrochloric acid to adjust the pH to 5-6, after adjustment, cool to 0-5°C, keep warm for crystallization for 24 hours, filter, and wash the filter cake with a small amount of acetone; add 2 times the amount of acetone to the obtained solid, heat and reflux to dissolve, keep warm for 15 minutes, filter, cool the filtrate to 0-5°C, keep warm for crystallization for 24 hours, filter, wash the filter cake with a small amount of acetone, repeat this operation once, and vacuum dry the obtained solid to obtain articaine hydrochloride.

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

[0034] The invention recovers concentrated ethyl acetate generated in the process of extracting articaine hydrochloride with ethyl acetate as an organic solvent to obtain recovered ethyl acetate with high recovery rate and purity, and then the recovered ethyl acetate is further applied to the extraction process of articaine hydrochloride, and the extraction effect thereof can reach the extraction effect of new ethyl acetate, thereby improving the reuse 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 invention are described clearly and completely below. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. 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.

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

[0037] Example 1

[0038] Preparation of recovered ethyl acetate.

[0039] Step 1: adding a 0.1 mol / L hydrochloric acid solution to 1 kg of concentrated ethyl acetate produced in the process of extracting articaine hydrochloride with ethyl acetate as an organic solvent, adjusting the pH to 4, stirring for 10 min, and then standing for 25 min to separate, to obtain an organic phase 1;

[0040] Step 2: Wash the organic phase 1 with 100 g of purified water, stir it for 10 min, and then let it stand for 25 min to separate the layers to obtain an organic phase 2; concentrate the organic phase 2 using a reduced pressure vacuum concentration method (vacuum degree -0.08 MPa, collection temperature 45°C), collect the fractions, and obtain recovered ethyl acetate.

[0041] After weighing, the mass of ethyl acetate is 850g. After calculation, the recovery rate of ethyl acetate is 85%. After testing, the purity of ethyl acetate is 99.9% (standard content ≥99.5%).

[0042] Example 2

[0043] Preparation of recovered ethyl acetate.

[0044] The preparation process is compared with Example 1, except that in step 1, 0.1 mol / L hydrochloric acid solution is replaced by 0.1 mol / L phosphoric acid aqueous solution, and other conditions are exactly the same, and finally recovered ethyl acetate is obtained.

[0045] After weighing, the mass of ethyl acetate was 849 g. After calculation, the recovery rate of ethyl acetate was 84.9%. After testing, the purity of ethyl acetate was 99.6%.

[0046] Example 3

[0047] Preparation of recovered ethyl acetate.

[0048] The preparation process is different from that in Example 1, except that in step 1, 0.1 mol / L hydrochloric acid solution is replaced by 0.1 mol / L acetic acid aqueous solution, and other conditions are exactly the same, and finally recovered ethyl acetate is obtained.

[0049] After weighing, the mass of ethyl acetate was 851 g. After calculation, the recovery rate of ethyl acetate was 85.1%. After testing, the purity of ethyl acetate was 99.5%.

[0050] Example 4

[0051] Preparation of recovered ethyl acetate.

[0052] The preparation process is compared with Example 1, except that in step 1, the 0.1 mol / L hydrochloric acid solution is replaced by a 0.1 mol / L sulfuric acid aqueous solution, and other conditions are exactly the same, and finally recovered ethyl acetate is obtained.

[0053] After weighing, the mass of ethyl acetate was 850 g. After calculation, the recovery rate of ethyl acetate was 85%. After testing, the purity of 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, which 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] By analyzing the data in Table 1, it can be known that the recovery rate of the recovered ethyl acetate obtained by recovering the concentrated ethyl acetate produced in the process of extracting articaine hydrochloride with ethyl acetate as the organic solvent using the recovery method of the present invention reaches about 85%, and the recovery rate is high. The purity reaches 99.5% and above, which meets the standard purity, so the recovered ethyl acetate can be reused.

[0058] Test Examples 1-4

[0059] Articaine hydrochloride was extracted using ethyl acetate as organic solvent.

[0060] The ethyl acetate recovered in Examples 1-4 was respectively used as an organic solvent in the extraction process of articaine hydrochloride to conduct four groups of experiments, and the experimental extraction process of each group was as follows.

[0061] Step 1: dissolve 100g of 4-methyl-3[[1-oxo-2-(chloro)-propyl]amino]-2-thiophenecarboxylic acid methyl ester in 300g of DMF, heat to 35°C to dissolve, start to drop 100mL of n-propylamine, control the temperature at 35°C, after the dropwise addition is completed, control the temperature at 35°C, and keep the reaction for 24h; after the reaction is completed, add 100g of recovered ethyl acetate and 100g of a prepared saturated aqueous solution of sodium carbonate to the feed liquid, stir for 20min, let stand for 30min to separate, and collect the organic phase and the aqueous phase separately;

[0062] Step 2: Add 200 g of recovered ethyl acetate to the collected aqueous phase again, stir for 20 min, let stand for 30 min to separate the layers, repeat this step once, collect the aqueous phase, and combine the organic phases; then add 10 g of anhydrous sodium sulfate to the collected combined organic phases, dry them, and concentrate them, evaporate the organic phase, and obtain an oily substance;

[0063] Step 3: Add 1.3 times the amount of acetone to the oily substance, stir and dissolve, control the temperature ≤40°C, use concentrated hydrochloric acid to adjust the pH to 5, after adjustment, cool to 3°C, keep warm for 24 hours to crystallize, filter, and wash the filter cake with 1 times the amount of acetone; add 2 times the amount of acetone to the solid obtained after washing, heat and reflux to dissolve, keep warm at 25°C for 15 minutes, filter, cool the filtrate to 3°C, keep warm for 24 hours to crystallize, filter, wash the filter cake with 1 times the amount of acetone, repeat this operation once, and the obtained solid is vacuum dried at 70°C for 8 hours to finally obtain articaine hydrochloride.

[0064] Comparative Example 1

[0065] Articaine hydrochloride was extracted using ethyl acetate as 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 used for the first time after purchase, with a purity of 99.8%), and other conditions are exactly the same, and articaine hydrochloride is finally obtained.

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

[0068] Table 2

[0069]

[0070]

[0071] By analyzing the data in Table 2, it can be learned that the yield and purity of the articaine hydrochloride obtained by extraction in Test Examples 1-4 are similar to those of the articaine hydrochloride obtained by extraction in Comparative Example 1, and both meet the use requirements; this shows that the recovered ethyl acetate obtained by the recovery method of the present invention is applied to the extraction process of articaine hydrochloride, which can achieve a better extraction effect.

[0072] The above are only preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for recovering ethyl acetate, characterized in that: The steps include: S1: adding an acidic aqueous solution to the concentrated ethyl acetate produced in the process of extracting articaine hydrochloride with ethyl acetate as an organic solvent to adjust the pH, and standing and stratifying after sufficient stirring to obtain an organic phase 1; S2: washing the organic phase 1 with purified water, stirring it fully and then standing it for stratification to obtain an organic phase 2; concentrating the organic phase 2, collecting the fractions, and obtaining recovered ethyl acetate.

2. The method for recovering ethyl acetate according to claim 1, wherein In step S1, the acidic aqueous solution includes a combination of one or more of hydrochloric acid, phosphoric acid, acetic acid and sulfuric acid.

3. The method for recovering ethyl acetate according to claim 2, wherein: The concentration of the acidic aqueous solution is 0.1 mol / L-1 mol / L.

4. The method for recovering ethyl acetate according to claim 1, wherein In step S1, when an acidic aqueous solution is added for pH adjustment, the pH value is adjusted to 1-6.

5. 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.

6. The method for recovering ethyl acetate according to claim 1, wherein: In step S2, the concentration treatment method is: using reduced pressure vacuum concentration method, the vacuum degree is - (0.04-0.10) MPa, and the collection temperature is 30°C-70°C.

7. The method for recovering ethyl acetate according to claim 6, wherein: The collection temperature is the feed liquid temperature of the organic phase 2 during reduced pressure vacuum concentration.

8. 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.

9. An application of the method for recovering ethyl acetate as claimed in any one of claims 1 to 8, characterized in that: The recovered ethyl acetate is applied to the extraction process of articaine hydrochloride.

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