阅读说明：本技术 一种溶剂回用的葡甲胺生产工艺 (Solvent-recycled meglumine production process ) 是由 卿文彬 张征彬 李琳 张来弟 周秋火 柏挺 华吉涛 于 2020-12-12 设计创作，主要内容包括：本申请涉及一种溶剂回用的葡甲胺生产工艺,其包括以下步骤：S1：一甲胺在无水乙醇中与葡萄糖进行缩合,得到息夫氏盐；S2：息夫氏盐中加入催化剂、无水乙醇,通入氢气反应得氢化物,结晶得固体氢化物和母液,分离固体的氢化物,然后融化氢化物并加入乙二胺四乙酸二钠,减压浓缩、甩滤得到葡甲胺粗品；S3：葡甲胺粗品在甲醇中重结晶,得甲醇母液和葡甲胺湿品,甲醇母液减压蒸馏得甲醇回收液；在步骤S2得到的母液中加入硫酸调PH至6-7,加入硅胶颗粒并持续搅拌混匀,然后过滤出硅胶颗粒,得到滤液,蒸馏得到乙醇回收液。本申请具有提高乙醇回收脱水效果的效果。(The application relates to a solvent-recycled meglumine production process, which comprises the following steps: s1: condensing monomethylamine with glucose in absolute ethyl alcohol to obtain a Schiff's salt; s2: adding a catalyst and absolute ethyl alcohol into the Schiff's salt, introducing hydrogen to react to obtain hydride, crystallizing to obtain solid hydride and mother liquor, separating the solid hydride, melting the hydride, adding disodium edetate, concentrating under reduced pressure, and performing spin filtration to obtain a meglumine crude product; s3: recrystallizing the meglumine crude product in methanol to obtain methanol mother liquor and a meglumine wet product, and distilling the methanol mother liquor under reduced pressure to obtain methanol recovery solution; and (4) adding sulfuric acid into the mother liquor obtained in the step S2 to adjust the pH value to 6-7, adding silica gel particles, continuously stirring and uniformly mixing, filtering the silica gel particles to obtain filtrate, and distilling to obtain an ethanol recovery solution. The application has the effect of improving the ethanol recovery dehydration effect.)

1. A solvent recycling meglumine production process is characterized in that: the method comprises the following steps:

s1: condensing monomethylamine with glucose in absolute ethyl alcohol to obtain a Schiff's salt;

s2: adding a catalyst and absolute ethyl alcohol into the Schiff's salt, introducing hydrogen to react to obtain hydride, crystallizing to obtain solid hydride and mother liquor, separating the solid hydride, melting the hydride, adding disodium edetate, concentrating under reduced pressure, and performing spin filtration to obtain a meglumine crude product;

s3: recrystallizing the meglumine crude product in methanol to obtain methanol mother liquor and a meglumine wet product, and distilling the methanol mother liquor under reduced pressure to obtain methanol recovery solution;

and (4) adding sulfuric acid into the mother liquor obtained in the step S2 to adjust the pH value to 6-7, adding silica gel particles, continuously stirring and uniformly mixing, filtering the silica gel particles to obtain filtrate, and distilling to obtain an ethanol recovery solution.

2. The process for producing meglumine with recycled solvent according to claim 1, wherein the process comprises the following steps: the mass ratio of the silica gel to the mother liquor is 1: (2-4).

3. The process for producing meglumine with recycled solvent according to claim 1, wherein the process comprises the following steps: and adding silica gel particles into the mother liquor, and stirring and uniformly mixing for 5-20 min.

4. The process for producing meglumine with recycled solvent according to claim 1, wherein the process comprises the following steps: calcium oxide is added to the filtrate.

5. The process for producing meglumine with recycled solvent according to claim 4, wherein the process comprises the following steps: and when the calcium oxide is added, stirring until the calcium oxide does not react any more, and continuously adding the calcium oxide.

6. The process for producing meglumine with recycled solvent according to claim 4, wherein the process comprises the following steps: after the calcium oxide is added, 98wt% concentrated sulfuric acid is added until the pH is 6-7.

7. The process for producing meglumine with recycled solvent according to claim 4, wherein the process comprises the following steps: after the calcium oxide is added until no reaction occurs, the mass ratio of the calcium oxide to the concentrated sulfuric acid which is continuously added is 1: (1.85-2.25).

8. The process for producing meglumine with recycled solvent according to claim 1, wherein the process comprises the following steps: and drying the silica gel particles filtered from the mother solution at the temperature of 100 ℃ and 110 ℃ for 1-2 h.

Technical Field

The application relates to the field of production of meglumine, in particular to a production process of meglumine by recycling a solvent.

Background

Meglumine, also called glucamine or 1-deoxy-1-methylamine sorbitol, is used for preparing contrast agents, such as diatrizoate and meglumine cholate, and also used as an auxiliary material or an intermediate of other medicines.

In the related technology, glucose and methylamine are condensed into a salt of Schiff's in absolute ethyl alcohol, and the salt is synthesized into meglumine by taking hydrogen as a hydrogen source and Raney nickel as a catalyst, and then the product is obtained by catalytic hydrogenation.

The absolute ethyl alcohol is used as a solvent, and can be reused only by distilling and dehydrating, so that the dehydration effect is poor, and only a small proportion of ethyl alcohol can be recycled.

Disclosure of Invention

In order to improve the dehydration effect, the application provides a solvent-recycled meglumine production process.

The application provides a solvent recycling meglumine production process, which adopts the following technical scheme:

a solvent-recycled meglumine production process comprises the following steps:

s1: condensing monomethylamine with glucose in absolute ethyl alcohol to obtain a Schiff's salt;

s2: adding a catalyst and absolute ethyl alcohol into the Schiff's salt, introducing hydrogen to react to obtain hydride, crystallizing to obtain solid hydride and mother liquor, separating the solid hydride, melting the hydride, adding disodium edetate, concentrating under reduced pressure, and performing spin filtration to obtain a meglumine crude product;

s3: recrystallizing the meglumine crude product in methanol to obtain methanol mother liquor and a meglumine wet product, and distilling the methanol mother liquor under reduced pressure to obtain methanol recovery solution;

and (4) adding sulfuric acid into the mother liquor obtained in the step S2 to adjust the pH value to 6-7, adding silica gel particles, continuously stirring and uniformly mixing, filtering the silica gel particles to obtain filtrate, and distilling to obtain an ethanol recovery solution.

By adopting the technical scheme, the PH is adjusted, so that the mother liquor is basically in a neutral environment, the silica gel particles can absorb moisture in the mother liquor, the content of the moisture in the mother liquor is reduced, the water content in the mother liquor is greatly reduced, the mother liquor basically cannot damage the silica gel, the silica gel can be repeatedly utilized, and meanwhile, the silica gel particles can also adsorb other trace organic matter impurities and the like in the mother liquor, so that the purity of the ethanol recovery liquid is improved; then, distillation is carried out, so that the recovered ethanol solution has high purity, the recovery rate is improved, and the removal of water in advance can properly increase the distillation temperature and is beneficial to increasing the recovery rate of ethanol; the silica gel particles can be reused, so that the recycling cost of the ethanol is reduced;

in the whole production process, only two solvents, namely absolute ethyl alcohol and methanol, are used, the ethyl alcohol can be recovered with high quality through the recovery mode, and the methanol recovery solution can be reused, so that zero emission is basically realized in the whole production process of the meglumine, and the production process is more environment-friendly.

Optionally, the mass ratio of the silica gel to the mother liquor is 1: (2-4).

Through adopting above-mentioned technical scheme, under this condition, silica gel can be comparatively clean with the water absorption in the mother liquor to the distillation is more quick, and the power consumption is lower.

Optionally, after adding the silica gel particles into the mother liquor, stirring and uniformly mixing for 5-20 min.

By adopting the technical scheme, the distillation temperature of the filtrate is 80-85 ℃, when the liquid level is reduced to 1/5, the distillation temperature is 85-95 ℃, and the distillation is finished until the liquid level does not fluctuate greatly.

Optionally, calcium oxide is added to the filtrate.

By adopting the technical scheme, the calcium oxide reacts with the residual small amount of water, so that the water in the filtrate is further removed; the silica gel particles and the calcium oxide are used together, and the silica gel particles can be dried, recycled and reused after being used, so that the consumption of the calcium oxide is greatly reduced, and the cost is reduced; and the dosage of the calcium oxide is less, and the consumption of the calcium oxide is reduced.

Optionally, the calcium oxide is added while stirring until the calcium oxide does not react any more, and then the calcium oxide is continuously added.

By adopting the technical scheme, the calcium oxide is excessive, so that the moisture is removed more cleanly.

Optionally, after the calcium oxide is added, 98wt% concentrated sulfuric acid is added until the pH is 6-7.

By adopting the technical scheme, the filtrate is strong alkaline, the PH is adjusted to 6-7, and the recovery rate of the ethanol is improved; and the calcium oxide reacts with water to obtain calcium hydroxide, the sulfuric acid reacts with the calcium hydroxide and hydroxide radicals from other sources in the filtrate, and then a very small amount of water carried in the sulfuric acid can be removed by redundant calcium oxide, so that the purity of the ethanol recovery solution is ensured.

Optionally, after the calcium oxide is added until no reaction occurs, the mass ratio of the calcium oxide to the concentrated sulfuric acid which is continuously added is 1: (1.85-2.25).

Through adopting above-mentioned technical scheme, the addition of silica gel granule for the quantity of calcium oxide reduces, thereby the calcium hydroxide that produces reduces, when making the later stage use sulphuric acid to adjust PH, and the quantity that sulphuric acid is used for neutralizing calcium hydroxide reduces, and the quantity of sulphuric acid reduces, further reduce cost.

Optionally, the silica gel particles filtered out from the mother solution are dried for 1-2h at the temperature of 100-110 ℃.

By adopting the technical scheme, the silica gel particles are dried, the moisture contained in the silica gel particles is evaporated, and the silica gel particles can be reused and used for removing the moisture in the filtrate.

In summary, the present application includes at least one of the following beneficial technical effects:

the content of water in the mother liquor is reduced, the water content in the mother liquor is greatly reduced, and the recovered ethanol solution obtained by recovery has higher purity; the ethanol recovery cost is reduced and the recovery rate is improved by controlling the silica gel energy, the addition of quicklime, the adjustment of the pH value by sulfuric acid and the like; in the whole production process of the meglumine, zero emission is basically realized, and the method is more environment-friendly.

Detailed Description

The present application is described in further detail in conjunction with the following.

Glucose, pharmaceutical grade, the manufacturer is the limited company of Xian Tianzheng pharmaceutic adjuvant;

monomethylamine was manufactured by Zhengzhou xing dao chemical technology ltd;

absolute ethyl alcohol, pharmaceutical grade, model YF-841, Brand Kangyuan, purchased from Yongfa City trade Co., Ltd;

disodium ethylene diamine tetraacetate, pharmaceutical grade, is from Shanxi Zhengyi pharmaceutical adjuvant Co., Ltd;

methanol, pharmaceutical grade, available from riverine energy resins limited.

Example 1

The preparation steps of the catalyst are as follows: melting 50g of aluminum at 800 ℃, melting 7g of rhodium, 40g of nickel and 3g of chromium at 2500 ℃, adding the molten rhodium, nickel and chromium into the molten aluminum, uniformly stirring, cooling, melting, spraying and quenching the alloy by adopting a spraying method to obtain the aluminum nickel chromium rhodium alloy, and screening the aluminum nickel chromium rhodium alloy with the particle size of 80-100 meshes.

Then stirring 25wt% sodium hydroxide solution, heating to 43 ℃, and gradually adding aluminum nickel chromium rhodium alloy powder, wherein the mass ratio of the aluminum nickel chromium rhodium alloy to the alkali liquor is 1: and 5, naturally heating to 90 ℃, keeping the temperature for 2.6 hours, cooling to 60 ℃, stopping stirring, repeatedly washing with water until the pH is 7, washing with absolute ethyl alcohol until the content of the ethyl alcohol in the feed liquid is 96%, and discharging.

A solvent-recycled meglumine production process comprises the following steps:

s1: introducing monomethylamine gas into absolute ethyl alcohol at 40 ℃ and under the pressure of 0.25MPa to prepare monomethylamine absolute ethyl alcohol solution, and then adding 110Kg of glucose while stirring, wherein the weight ratio of the glucose to the absolute ethyl alcohol to the monomethylamine is 1: 3.27: 0.38, heating after adding, and controlling the temperature to 47 ℃ to dissolve glucose to obtain the salt of the Schiff's family;

s2: adding a catalyst and absolute ethyl alcohol into a Schff's salt, removing air, stirring, heating, introducing hydrogen when the temperature reaches 45 ℃, controlling the temperature at 55 ℃, introducing hydrogen under the pressure of 0.32Mpa until hydrogen is not absorbed any more, removing residual hydrogen in a kettle, crystallizing to obtain a solid hydride and a mother solution, separating the solid hydride, adding water into the solid hydride to melt the hydride, standing for 73 hours, adding ethylene diamine tetraacetic acid, heating to 55 ℃, keeping the temperature for 0.85 hours, then carrying out suction filtration on the liquid by using a sand stick, then carrying out reduced pressure concentration on the liquid under the vacuum condition of 0.07Mpa until the liquid is a viscous jelly, adding methanol, stirring, cooling and crystallizing at 4 ℃, carrying out suction filtration and washing to obtain a meglumine crude product, and purifying the meglumine crude product. In the step, the mass ratio of the sodium benzoate to the hydrogen to the absolute ethyl alcohol is 1: 0.01: 0.08: 0.02: 0.58, wherein the mass ratio of the solid hydride to the ethylene diamine tetraacetic acid and the methanol is 1: 0.004: 0.33.

the air removal process comprises the following steps: introducing nitrogen gas to drive off the air in the kettle at 0.1, 0.15 and 0.2Mpa respectively, and introducing hydrogen gas to drive off the nitrogen in the kettle at 0.1, 0.15 and 0.2Mpa respectively after the air is driven off.

S3: dissolving the meglumine crude product in water, wherein the weight ratio of the meglumine crude product to the water is 1: 2.21, sampling to detect nickel salt, if the nickel salt is positive, gradually adding ethylene diamine tetraacetic acid until the detection result of the nickel salt is negative, standing overnight after the detection result is negative, and filtering to obtain filtrate;

concentrating the filtrate under reduced pressure under 0.07Mpa until it is viscous jelly, adding methanol, and stirring to obtain meglumine crude product and methanol at weight ratio of 1: 2) and then cooling, crystallizing, filtering and washing to obtain a methanol mother liquor and a wet meglumine product, feeding the wet meglumine product into a flow-through dryer for drying at 87 ℃ for 6 hours, cooling to 35 ℃, and discharging to obtain a final meglumine product.

And further carrying out reduced pressure concentration on the methanol mother liquor under the vacuum degree of 0.08Mpa to obtain a methanol recovery liquor, wherein the methanol recovery liquor can be recycled and added into the filtrate after the reduced pressure concentration.

Adding sulfuric acid into the mother liquor obtained in the step S2 to adjust the pH value to 6, and adding silica gel particles, wherein the mass ratio of the silica gel to the mother liquor is 1: and 4, continuously stirring and uniformly mixing for 5min, filtering out silica gel particles to obtain filtrate, adding calcium oxide into the filtrate at a constant speed, continuously stirring until the calcium oxide does not react any more, continuously adding the calcium oxide, wherein the mass ratio of the continuously added calcium oxide to concentrated sulfuric acid is 1: 2.25, after the calcium oxide is added, adding 98wt% concentrated sulfuric acid until the pH value is 6, and distilling to obtain an ethanol recovery solution.

Drying the filtered silica gel particles in the mother liquor for 1h at 110 ℃ and then continuously drying the mother liquor.

Example 2

The difference from example 1 is that:

adding sulfuric acid into the mother liquor obtained in the step S2 to adjust the pH value to 7, and adding silica gel particles, wherein the mass ratio of the silica gel to the mother liquor is 1: 2.2, continuously stirring and uniformly mixing for 10min, filtering out silica gel particles to obtain a filtrate, adding calcium oxide into the filtrate at a constant speed, continuously stirring until the calcium oxide does not react any more, continuously adding the calcium oxide, wherein the mass ratio of the continuously added calcium oxide to concentrated sulfuric acid is 1: and 2, after the calcium oxide is added, adding 98wt% concentrated sulfuric acid until the pH value is 7, and distilling to obtain an ethanol recovery solution.

Drying the silica gel particles filtered from the mother liquor at 105 ℃ for 1.5h, and then continuously drying the mother liquor.

Example 3

The difference from example 1 is that:

adding sulfuric acid into the mother liquor obtained in the step S2 to adjust the pH value to 7, and adding silica gel particles, wherein the mass ratio of the silica gel to the mother liquor is 1: 2, continuously stirring and uniformly mixing for 20min, filtering out silica gel particles to obtain filtrate, adding calcium oxide into the filtrate at a constant speed, continuously stirring until the calcium oxide does not react any more, continuously adding the calcium oxide, wherein the mass ratio of the continuously added calcium oxide to concentrated sulfuric acid is 1: 1.85, after the calcium oxide is added, adding 98wt% concentrated sulfuric acid until the pH value is 7, and distilling to obtain an ethanol recovery solution.

Drying the silica gel particles filtered from the mother liquor at 100 ℃ for 2h, and then continuously drying the mother liquor.

Example 4

The difference from example 2 is that: and (3) filtering out silica gel particles to obtain filtrate, and directly adding concentrated sulfuric acid for pH adjustment without adding calcium oxide.

Example 5

The difference from example 2 is that: in the filtrate, after the addition of calcium oxide was completed, no sulfuric acid was added for PH adjustment.

Example 6

The difference from example 2 is that: the mass ratio of the calcium oxide to the concentrated sulfuric acid which are continuously added is 1: 1.5.

comparative example 1

The difference from example 2 is that: no silica gel particles were added.

Comparative example 2

The difference from example 2 is that: no pH adjustment was performed before the addition of the silica gel particles.

Performance detection

The mass fraction (%) of ethanol in the ethanol recovery solution obtained in the mother liquor, examples 1 to 6 and comparative examples 1 to 2 was measured according to GB/T9722-2006 "general rules of gas chromatography", and the mass fraction is larger and the purity is higher, the mass fraction (%) of ethanol in the ethanol recovery solution is recorded, and the ethanol yield = (mass fraction of ethanol in the ethanol recovery solution x volume of the ethanol recovery solution)/(mass fraction of ethanol in the mother liquor x volume of the mother liquor) is calculated and recorded;

the results are shown in Table 1.

TABLE 1 Performance test results

	Mass fraction/%	Yield/%
			Example 1	89.5	78.3
Example 2	91.2	80.6
			Example 3	90.0	77.8
Example 4	85.4	81.1
			Example 5	91.0	80.4
Example 6	91.0	79.6
			Comparative example 1	82.3	74.8
Comparative example 2	78.5	79.8

As can be seen from Table 1, the mass fraction of ethanol and the yield of ethanol in the ethanol recovery solution obtained in examples 1-6 are higher than those in comparative example 1, so the process for recovering ethanol in the mother liquor is better.

The mass fraction and yield of the ethanol recovered from examples 1-6 were higher than those of comparative example 2 because the pH of the solution was not adjusted before the silica gel particles were added in comparative example 2, and the silica gel was also damaged in the alkaline mother liquor, and adsorption of water and other impurities was reduced, affecting the mass fraction and yield of ethanol in the ethanol recovered solution.

In examples 1 to 3, the yield and purity (mass fraction) of example 2 were the highest, so the process conditions for recovering ethanol from the mother liquor of example 2 were more excellent.

In examples 2 and 4, calcium oxide was not added in example 4, so that a small amount of water remained in the mother liquor, and then a small amount of water was introduced by adding sulfuric acid, so that the mass fraction of ethanol in the ethanol recovery solution of example 4 was decreased, but the yield was slightly increased.

In examples 2 and 5, the pH of the mother liquor may be slightly alkaline without pH adjustment after the calcium oxide is added in example 5, and the mass fraction of ethanol in the ethanol recovery solution is not substantially changed, but the yield of ethanol is slightly reduced.

In examples 2 and 6, the addition of calcium oxide in example 6 was excessive, and the mass fraction of ethanol and the yield of ethanol in the ethanol-recovered solution in example 6 were both slightly decreased, so the calcium oxide addition in the present application was more preferably limited.

The above embodiments are preferred embodiments of the present application, and the protection scope of the present application is not limited by the above embodiments, so: all equivalent changes made according to the structure, shape and principle of the present application shall be covered by the protection scope of the present application.