Preparation method of indigo carmine

Abstract

The invention discloses a preparation method of indigo carmine, which comprises the following steps: (1) adding indigo into chloralkane, stirring and controlling the temperature, and dropwise adding chlorosulfonic acid for sulfonation reaction; after the reaction is finished, controlling the temperature, adding deionized water, stirring, standing for layering, removing a lower-layer organic phase, adding liquid caustic soda into an upper-layer water phase under the temperature control, separating out a slurry solid until the pH value of a mixture of the slurry solid and the solution is greater than or equal to 13, cooling to be less than or equal to 10 DEG C, and filtering; washing the filter cake with cold deionized water and methanol in sequence to obtain an indigo carmine wet crude product; (2) adding the crude product obtained in the step (1) into deionized water, heating to 90 DEG C or above, completely dissolving the crude product, adding activated carbon, stirring, filtering while hot, carrying out reduced pressure distillation on filtrate, cooling to 10 DEG C or below, and filtering; and washing the filter cake with cold deionized water and acetone in sequence, and carrying out vacuum drying to obtain an indigo carmine product. The method has the advantages of simplicity in operation, high product yield, low cost and small amount of wastewater and waste solvent.

Description

Technical Field

[0001] This invention relates to the field of indigo carmine technology, and specifically to a method for preparing indigo carmine. Background Technology

[0002] Indigo carmine, chemical name: disodium 5,5′-indigo disulfonate, English name: Indigo carmine, CAS number: 860-22-0; molecular formula: C 16 H8N2Na2O8S2; Molecular weight: 466.37; Structural formula:

[0003] It is not only a food coloring agent but also used in cosmetics. In the medical field, it is used as a contrasting staining agent for mucous membranes, particularly suitable for the examination of the stomach and intestines, and its applications are very wide-ranging. The synthetic route reported in Chinese Patent CN 110023414 A is as follows:

[0004]

[0005] This process uses indigo as raw material, undergoing a sulfonation reaction in concentrated sulfuric acid. The sulfonic acid product is then purified, salted with sodium alkoxide, and subsequently oxidized to obtain indigo carmine product, with a yield of 39%.

[0006] This process uses 20 times the amount of sulfuric acid (molar amount) of indigo. Simultaneously, the sulfonation reaction produces a large amount of monosulfonated and polysulfonated byproducts. After the sulfonation reaction, the reaction solution is extracted into a large amount of water and solvent, generating a large amount of acidic wastewater. The sulfonated product undergoes a complex purification process (reduction with sodium dithionite, followed by multiple pulping and filtration operations with solvent). After purification, it is then salted with sodium alkoxide and oxidized with air to obtain the product indigo carmine. The product yield is low, with a reported yield of 39% based on indigo. The process is complex and generates a large amount of waste.

[0007] The synthetic route reported in World Patent WO2018 / 116325A1 is as follows:

[0008]

[0009] The process document describes using self-made indigo as raw material. The reaction is carried out in sulfuric acid at a temperature of 20-30°C for 1 hour. The reaction solution is then extracted into a mixed solvent to precipitate sulfonic acid products. After washing with methanol, the product is directly reacted with liquid alkali to form a salt without further purification. After filtration, crude indigo carmine is obtained. The crude product is then purified multiple times with a mixed solvent to obtain the finished indigo carmine product with a purity of 99.9% and a yield of 18%.

[0010] This process uses a large amount of sulfuric acid, 74 times the molar amount of indigo. The sulfonation extraction uses 90 times the solvent volume (relative to the weight of indigo), which will generate a large amount of waste acid solvent. The crude indigo carmine needs to be crystallized 5 times to meet the quality standards. The product yield is extremely low, only 18% based on indigo. Summary of the Invention

[0011] The technical problem to be solved by the present invention is to provide a method for preparing indigo carmine, in which chloroalkanes in the process can be recycled and reused, waste is reduced, operation is simple, and product yield is high.

[0012] To address the above technical problems, this invention discloses a method for preparing indigo carmine, the synthetic route of which is as follows:

[0013]

[0014] The method includes the following steps:

[0015] (1) First, add chloroalkanes to the reaction vessel, then add indigo, start stirring to form a slurry liquid, control and maintain the temperature at 20-30℃, add chlorosulfonic acid dropwise, and continue to keep the temperature for reaction after the addition is complete. The reaction time is generally 1 hour. After the reaction is complete, control the temperature at 20-30℃, slowly add deionized water, and stir thoroughly. After stirring, let it stand to separate into layers, remove the lower organic phase (chloroalkanes), and control the upper aqueous phase (sulfonic acid aqueous solution) at 20-30℃, and slowly add liquid alkali to precipitate a slurry solid until the pH of the mixture of slurry solid and solution is ≥13. Then cool to ≤10℃, filter, and collect the filter cake. Wash the obtained filter cake with cold deionized water and methanol in sequence to obtain wet crude indigo carmine.

[0016] (2) Add deionized water to the reaction vessel, then add the wet crude indigo carmine obtained in step (1), heat to above 90°C to completely dissolve the wet crude indigo carmine, add activated carbon, and stir thoroughly; after stirring, filter while hot, collect the filtrate, distill the obtained filtrate under reduced pressure, and after the amount of water distilled reaches 75-80% of the total amount of deionized water added, cool to ≤10°C, filter, and collect the filter cake; wash the obtained filter cake with cold deionized water and acetone in sequence, and then dry it under vacuum to obtain the indigo carmine product.

[0017] Furthermore, the chloroalkane mentioned in step (1) is selected from one or more chloroalkanes having 1 to 20 carbon atoms.

[0018] Furthermore, the chloroalkane mentioned in step (1) is selected from one or more of chloromethane, dichloromethane, chloroform, carbon tetrachloride, chloroethane, 1,2-dichloroethane, and 1,2-dichloropropane, preferably chloroform, dichloromethane, and 1,2-dichloroethane.

[0019] Furthermore, the mass ratio of indigo to chloroalkane in step (1) is 1:1 to 30, preferably 1:5.

[0020] Furthermore, the molar ratio of indigo to chlorosulfonic acid in step (1) is 1:2 to 2.5, preferably 1:2.1.

[0021] Furthermore, the cold deionized water mentioned in steps (1) and (2) is deionized water with a temperature ≤10℃.

[0022] Furthermore, the activated carbon in step (2) is pharmaceutical activated carbon, and its mass ratio with that of crude wet indigo carmine is 0.001 to 0.1:1, preferably 0.01:1.

[0023] Furthermore, the mass ratio of the wet crude indigo carmine to deionized water in step (2) is 1:12 to 30, preferably 1:16.

[0024] Furthermore, the mass ratio of the cold deionized water to the wet crude indigo carmine in step (2) is 0.5 to 5:1, preferably 1:1.

[0025] Furthermore, the mass ratio of acetone to crude indigo carmine wet product in step (2) is 0.5 to 5:1, preferably 1:1.

[0026] The beneficial effects of this invention are:

[0027] (1) Using chloroalkanes as solvent and chlorosulfonic acid in a certain molar amount for sulfonation reaction will not produce a large amount of waste acid and waste solvent, and the chloroalkanes in the process can be recycled.

[0028] (2) In the refining process, crude indigo carmine is dissolved by heating with deionized water and impurities are removed by activated carbon. The operation is simple, the cost is low, the product yield is high, and the product quality meets the standards. Detailed Implementation

[0029] The present invention will be further explained below with reference to the embodiments. The following embodiments are for illustrative purposes only and are not intended to limit the scope of the invention.

[0030] Example 1

[0031] First, add 100g of dichloromethane to a four-necked flask, then add 20g (0.076mol) of indigo. Start stirring to form a slurry. Control and maintain the temperature at 20℃, and add 18.2g (0.16mol) of chlorosulfonic acid dropwise. After the addition is complete, keep the mixture at this temperature for 1 hour. After the reaction is complete, control the temperature at 20℃ and slowly add 200g of deionized water, stirring for 30 minutes. After stirring, allow the mixture to stand and separate into layers. Remove the lower layer of dichloromethane. Control the temperature of the upper sulfonic acid aqueous solution at 30℃ and slowly add 30% liquid alkali. A slurry solid will precipitate. If the pH of the mixture of the slurry solid and the solution is ≥13, stop adding liquid alkali and cool to ≤10℃. Filter using a Buchner funnel and collect the filter cake. The obtained filter cake was washed once with 50g of deionized water at a temperature ≤10℃, and then washed once with 50g of methanol to obtain 50g of wet crude indigo carmine. The crude product content was sampled and tested. If the crude product content was <96%, the methanol washing operation was repeated until the crude product content was ≥96%.

[0032] Crude product purification: Add 800g of deionized water to a 1000mL four-necked flask, then add 50g of the above-obtained wet crude indigo carmine. Heat to 95℃ to completely dissolve the wet crude indigo carmine. Add 0.5g of pharmaceutical activated carbon and stir for 30 minutes. After stirring, filter while hot and collect the filtrate. Distill the filtrate under reduced pressure to obtain 600g of water. Cool to ≤10℃, filter, and collect the filter cake. Wash the obtained filter cake once with 50g of deionized water at ≤10℃, and then wash once with 50g of acetone to obtain 33.5g of wet indigo carmine. Take a sample to test the product content. If the product content is ≤99.0%, repeat the acetone washing operation until the product content is >99.0%. Then dry under vacuum at 60℃ for 8 hours to obtain 30.28g of finished indigo carmine with a product content of 99.9% and a yield of 85% based on indigo.

[0033] Example 2

[0034] First, add 100g of 1,2-dichloroethane to a four-necked flask, then add 20g (0.076mol) of indigo. Start stirring to form a slurry liquid. Control and maintain the temperature at 20℃, and add 18.2g (0.16mol) of chlorosulfonic acid dropwise. After the addition is complete, keep the reaction at this temperature for 1 hour. After the reaction is complete, control the temperature at 20℃ and slowly add 200g of deionized water, stirring for 30 minutes. After stirring, allow the mixture to stand and separate into layers. Remove the lower layer of 1,2-dichloroethane. Control the temperature of the upper sulfonic acid aqueous solution at 30℃ and slowly add 30% liquid alkali. A slurry solid will precipitate. If the pH of the mixture of the slurry solid and the solution is ≥13, stop adding liquid alkali and cool to ≤10℃. Filter using a Buchner funnel and collect the filter cake. The obtained filter cake was washed once with 50g of deionized water at a temperature ≤10℃, and then washed once with 50g of methanol to obtain 48g of wet crude indigo carmine. The crude product content was tested by sampling. If the crude product content was <96%, the methanol washing operation was repeated until the crude product content was ≥96%.

[0035] Crude product purification: Add 800g of deionized water to a 1000mL four-necked flask, then add 48g of the above-obtained wet crude indigo carmine. Heat to 95℃ to completely dissolve the wet crude indigo carmine. Add 0.5g of pharmaceutical activated carbon and stir for 30 minutes. After stirring, filter while hot and collect the filtrate. Distill the filtrate under reduced pressure to distill off 600g of water. Cool to ≤10℃, filter, and collect the filter cake. Wash the obtained filter cake once with 50g of deionized water at ≤10℃, and then wash once with 50g of acetone to obtain 32.8g of wet indigo carmine. Take a sample to test the product content. If the product content is ≤99.0%, repeat the acetone washing operation until the product content is >99.0%. Then dry under vacuum at 60℃ for 8 hours to obtain 29.54g of finished indigo carmine with a product content of 99.7% and a yield of 83% based on indigo.

[0036] Example 3

[0037] First, add 50g of 1,2-dichloroethane and 50g of dichloromethane to a four-necked flask, then add 20g (0.076mol) of indigo. Start stirring to form a slurry liquid. Control and maintain the temperature at 20℃, and add 18.2g (0.16mol) of chlorosulfonic acid dropwise. After the addition is complete, keep the reaction at this temperature for 1 hour. After the reaction is complete, control the temperature at 20℃ and slowly add 200g of deionized water, stirring for 30 minutes. After stirring, allow the mixture to stand and separate into layers. Remove the lower layer of dichloromethane and 1,2-dichloroethane mixture. Control the temperature of the upper sulfonic acid aqueous solution at 30℃ and slowly add 30% liquid alkali. A slurry solid will precipitate. If the pH of the mixture of the slurry solid and the solution is ≥13, stop adding liquid alkali and cool to ≤10℃. Filter using a Buchner funnel and collect the filter cake. The obtained filter cake was washed once with 50g of deionized water at a temperature ≤10℃, and then washed once with 50g of methanol to obtain 49g of wet crude indigo carmine. The crude product content was sampled and tested. If the crude product content was <96%, the methanol washing operation was repeated until the crude product content was ≥96%.

[0038] Crude product purification: Add 800g of deionized water to a 1000mL four-necked flask, then add 49g of the above-obtained wet crude indigo carmine. Heat to 95℃ to completely dissolve the wet crude indigo carmine. Add 0.5g of pharmaceutical activated carbon and stir for 30 minutes. After stirring, filter while hot and collect the filtrate. Distill the filtrate under reduced pressure to distill off 600g of water. Cool to ≤10℃, filter, and collect the filter cake. Wash the obtained filter cake once with 50g of deionized water at ≤10℃, and then wash once with 50g of acetone to obtain 32.4g of wet indigo carmine. Take a sample to test the product content. If the product content is ≤99.0%, repeat the acetone washing operation until the product content is >99.0%. Then dry under vacuum at 60℃ for 8 hours to obtain 29.87g of finished indigo carmine with a product content of 99.8% and a yield of 84% based on indigo.

[0039] Example 4

[0040] First, add 200g of 1,2-dichloropropane to a four-necked flask, then add 20g (0.076mol) of indigo. Start stirring to form a slurry liquid. Control and maintain the temperature at 20℃, and add 20.37g (0.175mol) of chlorosulfonic acid dropwise. After the addition is complete, keep the reaction at this temperature for 1 hour. After the reaction is complete, control the temperature at 20℃ and slowly add 200g of deionized water, stirring for 30 minutes. After stirring, allow the mixture to stand and separate into layers. Remove the lower layer of 1,2-dichloropropane. Control the temperature of the upper sulfonic acid aqueous solution at 30℃ and slowly add 30% liquid alkali. A slurry solid will precipitate. If the pH of the mixture of the slurry solid and the solution is ≥13, stop adding liquid alkali and cool to ≤10℃. Filter using a Buchner funnel and collect the filter cake. The obtained filter cake was washed once with 50g of deionized water at a temperature ≤10℃, and then washed once with 50g of methanol to obtain 45g of wet crude indigo carmine. The crude product content was tested. If the crude product content was <96%, the methanol washing operation was repeated until the crude product content was ≥96%.

[0041] Crude product purification: Add 1000g of deionized water to a 1500mL four-necked flask, then add 45g of the above-obtained wet crude indigo carmine. Heat to 95℃ to completely dissolve the wet crude indigo carmine. Add 1.0g of pharmaceutical activated carbon and stir for 30 minutes. After stirring, filter while hot and collect the filtrate. Distill the filtrate under reduced pressure to distill off 800g of water. Cool to ≤10℃, filter, and collect the filter cake. Wash the obtained filter cake once with 100g of deionized water at ≤10℃, and then wash once with 50g of acetone to obtain 29.7g of wet indigo carmine. Take a sample to test the product content. If the product content is ≤99.0%, repeat the acetone washing operation until the product content is >99.0%. Then dry under vacuum at 60℃ for 8 hours to obtain 27.67g of finished indigo carmine with a product content of 99.8% and a yield of 77.8% based on indigo.

[0042] Example 5

[0043] First, add 100g of carbon tetrachloride to a four-necked flask, then add 20g (0.076mol) of the indigo obtained above. Start stirring to form a slurry liquid. Control and maintain the temperature at 20℃, and add 18.2g (0.160mol) of chlorosulfonic acid dropwise. After the addition is complete, keep the reaction at this temperature for 1 hour. After the reaction is complete, control the temperature at 20℃ and slowly add 200g of deionized water, stirring for 30 minutes. After stirring, allow the mixture to stand and separate into layers. Remove the lower layer of carbon tetrachloride. Control the temperature of the upper sulfonic acid aqueous solution at 30℃ and slowly add 30% liquid alkali. A slurry solid will precipitate. If the pH of the mixture of the slurry solid and the solution is detected to be ≥13, stop adding liquid alkali and cool to ≤10℃. Filter using a Buchner funnel and collect the filter cake. The obtained filter cake was washed once with 50g of deionized water at a temperature ≤10℃, and then washed once with 50g of methanol to obtain 45g of wet crude indigo carmine. The crude product content was sampled and tested. If the crude product content was <96%, the methanol washing operation was repeated until the crude product content was ≥96%.

[0044] Crude product purification: Add 1000g of deionized water to a 1500mL four-necked flask, then add 45g of the above-obtained wet crude indigo carmine. Heat to 95℃ to completely dissolve the wet crude indigo carmine. Add 1.0g of pharmaceutical activated carbon and stir for 30 minutes. After stirring, filter while hot and collect the filtrate. Distill the filtrate under reduced pressure to obtain 800g of water. Cool to ≤10℃, filter, and collect the filter cake. Wash the obtained filter cake once with 100g of deionized water at ≤10℃, and then wash once with 50g of acetone to obtain 30.04g of wet indigo carmine. Take a sample to test the product content. If the product content is ≤99.0%, repeat the acetone washing operation until the product content is >99.0%. Then dry under vacuum at 60℃ for 8 hours to obtain 28.98g of finished indigo carmine with a product content of 99.8% and a yield of 81.5% based on indigo.

[0045] Example 6

[0046] First, add 100g of chloroform to a four-necked flask, then add 20g (0.076mol) of indigo. Start stirring to form a slurry. Control and maintain the temperature at 20℃, and add 18.2g (0.160mol) of chlorosulfonic acid dropwise. After the addition is complete, keep the reaction at this temperature for 1 hour. After the reaction is complete, control the temperature at 20℃ and slowly add 200g of deionized water, stirring for 30 minutes. After stirring, allow the mixture to stand and separate into layers. Remove the lower layer of chloroform. Control the temperature of the upper sulfonic acid aqueous solution at 30℃ and slowly add 30% liquid alkali. A slurry solid will precipitate. If the pH of the mixture of the slurry solid and the solution is ≥13, stop adding liquid alkali and cool to ≤10℃. Filter using a Buchner funnel and collect the filter cake. The obtained filter cake was washed once with 50g of deionized water at a temperature ≤10℃, and then washed once with 50g of methanol to obtain 45g of wet crude indigo carmine. The crude product content was sampled and tested. If the crude product content was <96%, the methanol washing operation was repeated until the crude product content was ≥96%.

[0047] Crude product purification: Add 1000g of deionized water to a 1500mL four-necked flask, then add 45g of the above-obtained wet crude indigo carmine. Heat to 95℃ to completely dissolve the wet crude indigo carmine. Add 1.0g of pharmaceutical activated carbon and stir for 30 minutes. After stirring, filter while hot and collect the filtrate. Distill the filtrate under reduced pressure to obtain 800g of water. Cool to ≤10℃, filter, and collect the filter cake. Wash the obtained filter cake once with 100g of deionized water at ≤10℃, and then wash once with 50g of acetone to obtain 31.08g of wet indigo carmine. Take a sample to test the product content. If the product content is ≤99.0%, repeat the acetone washing operation until the product content is >99.0%. Then dry under vacuum at 60℃ for 8 hours to obtain 29.66g of finished indigo carmine with a product content of 99.7% and a yield of 83.4% based on indigo.

[0048] Of course, the present invention may have other various embodiments. Without departing from the spirit and essence of the present invention, those skilled in the art can make various corresponding changes and modifications according to the present invention, but these corresponding changes and modifications should all fall within the protection scope of the claims of the present invention.

Claims

1. A method for preparing indigo carmine, characterized in that, Includes the following steps: (1) First, add chloroalkanes to the reaction vessel, then add indigo, start stirring, control and maintain the temperature at 20-30℃, add chlorosulfonic acid dropwise, and continue to keep the temperature for reaction after the addition is complete; after the reaction is complete, control the temperature at 20-30℃, slowly add deionized water, and stir thoroughly; after stirring is complete, let stand to separate the layers, remove the lower organic phase, control the temperature of the upper aqueous phase at 20-30℃, and slowly add liquid alkali to precipitate a slurry solid until the pH of the mixture of slurry solid and solution is ≥13, then cool to ≤10℃, filter, and collect the filter cake; wash the obtained filter cake with cold deionized water and methanol in sequence to obtain wet crude indigo carmine; (2) Add deionized water to the reaction vessel, then add the wet crude indigo carmine obtained in step (1), heat to above 90°C to completely dissolve the wet crude indigo carmine, add activated carbon, and stir thoroughly; after stirring, filter while hot, collect the filtrate, distill the obtained filtrate under reduced pressure, and after the amount of water distilled reaches 75-80% of the total amount of deionized water added, cool to ≤10°C, filter, and collect the filter cake; wash the obtained filter cake with cold deionized water and acetone in sequence, and then dry it under vacuum to obtain the indigo carmine product.

2. The preparation method according to claim 1, characterized in that, The chloroalkane mentioned in step (1) is selected from one or more chloroalkanes with 1 to 20 carbon atoms.

3. The preparation method according to claim 2, characterized in that, The chloroalkane mentioned in step (1) is selected from one or more of chloromethane, dichloromethane, chloroform, carbon tetrachloride, chloroethane, 1,2-dichloroethane, and 1,2-dichloropropane.

4. The preparation method according to claim 1, characterized in that, The mass ratio of indigo to chloroalkanes in step (1) is 1:1 to 30.

5. The preparation method according to claim 1 or 4, characterized in that, The molar ratio of indigo to chlorosulfonic acid in step (1) is 1:2 to 2.

5.

6. The preparation method according to claim 1, characterized in that, The cold deionized water mentioned in steps (1) and (2) is deionized water with a temperature ≤10℃.

7. The preparation method according to claim 1, characterized in that, The activated carbon mentioned in step (2) is pharmaceutical activated carbon, and its mass ratio with that of wet crude indigo carmine is 0.001 to 0.1:

1.

8. The preparation method according to claim 1 or 7, characterized in that, The mass ratio of the wet crude indigo carmine to deionized water in step (2) is 1:12-30.

9. The preparation method according to claim 8, characterized in that, The mass ratio of cold deionized water to wet crude indigo carmine in step (2) is 0.5 to 5:

1.

10. The preparation method according to claim 9, characterized in that, The mass ratio of acetone to crude indigo carmine wet product in step (2) is 0.5 to 5:1.

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