Preparation method of 2-aminoglycerol

Abstract

The invention relates to the technical field of organic synthesis, and discloses a preparation method of 2-aminoglycerol, which is characterized in that serinol is prepared by taking nitromethane and paraformaldehyde as raw materials, an effective solvent as a medium, a metal catalyst taking an inorganic matter as a carrier and hydrogen as a reducing agent by means of orthogonal design, single factor test and the like. And purifying by adopting high-vacuum distillation, and determining various parameters such as the ratio, the reaction temperature, the heat preservation time, the crystallization time, the hydrogen pressure, the vacuum degree and the like of various raw materials in the whole process. On the basis of a small-scale test process of the 2-aminoglycerol, further optimization is carried out, hydrogenation reaction conditions are optimized, salt forming process steps are reduced, the yield of the 2-aminoglycerol is increased to 80%, the product quality meets the export quality requirement, no obvious amplification effect exists, the equipment requirement is simple, the product quality is safe and stable, and large-scale production can be carried out in time; and further popularization and application are carried out.

Description

Technical Field

[0001] The invention relates to the technical field of organic synthesis, and in particular to a method for preparing 2-aminoglycerol. Background Art

[0002] Aminoglycerol (3-amino-1,2-propanediol) is mainly used to produce X-CT non-ionic contrast agent iohexol and is one of the main raw materials in the production and synthesis of iohexol. In the 1980s and before, the contrast agent market in the world used ionic X-ray contrast agents. Although ionic contrast agents effectively solved the problem of contrast density, this high-permeability contrast agent will also cause an increase in blood volume and vasodilation in the blood vessels, increase pulmonary venous pressure, vascular endothelial damage, and high neurotoxicity. Therefore, from the perspective of human safety, people have increasingly recognized and accepted the widespread use of non-ionic contrast agents. Since the beginning of this century, non-ionic contrast agent iohexol has entered hospitals in developed countries around the world and has officially entered the clinical use of medicine. At present, the preparation method of aminoglycerol has a variety of production processes according to the different raw materials used, such as cyclopropane method, chloroglycerol method, glycidol method, glyceraldehyde method, amination agent ammonia method, etc., and the production process is different, such as low-pressure method, medium-pressure method, high-temperature and high-pressure method, or continuous method and intermittent method, etc.

[0003] However, the salt-forming process steps in the existing preparation method of 2-aminoglycerol are too complicated, which leads to a significant reduction in the yield of 2-aminoglycerol. Summary of the invention

[0004] 1. Technical issues to be resolved

[0005] In view of the deficiencies in the prior art, the present invention provides a method for preparing 2-aminoglycerol, which has the advantages of optimizing hydrogenation reaction conditions, reducing salt-forming process steps, and improving the yield of 2-aminoglycerol, and solves the problem that the salt-forming process steps are too complicated, thereby greatly reducing the yield of 2-aminoglycerol.

[0006] (II) Technical solution

[0007] In order to achieve the above-mentioned purpose of increasing the yield of 2-aminoglycerol, the present invention provides the following technical scheme: a method for preparing 2-aminoglycerol, comprising the following steps:

[0008] S1. Condensation process

[0009] Add drinking water paraformaldehyde, negative methane and alkali solution into the reactor for condensation reaction, then add alkali solution and methanol to generate crystals, add methanol again after centrifugation, centrifuge and dry, then transfer to the hydrogenation batching kettle;

[0010] S2. Hydrogenation process

[0011] Methanol and ammonium salt are added to the hydrogenation batching kettle, and then a catalyst and hydrogen are added to the hydrogenation batching kettle for hydrogenation reaction, and the hydrogen in the hydrogenation batching kettle is replaced with nitrogen. After the hydrogenation reaction is completed, nitrogen is added to perform a second replacement of the hydrogen in the hydrogenation batching kettle;

[0012] S3. Distillation process

[0013] The hydrogenation reaction liquid after substitution is pumped into a concentration kettle, the methanol in the concentration kettle is recovered by distillation at room temperature, isopropanol is added to the concentration kettle for filtration, and the reaction is performed to obtain a crude 2-aminoglycerol product;

[0014] S4, Refining process

[0015] Add isopropanol into the recrystallization kettle, stir, and centrifuge to obtain 2-aminoglycerol wet material;

[0016] S5. Drying process

[0017] The wet 2-aminoglycerol material is put into a double cone vacuum dryer for vacuum drying to obtain a finished 2-aminoglycerol product;

[0018] Preferably, in step S1, drinking water and paraformaldehyde are added to the reactor, stirring is started, nitromethane is added, cooling water is turned on to cool to 25°C, a small amount of liquid alkali is added to the reactor, and the reaction is kept warm for 6-8 hours, the temperature is controlled below 25°C, liquid alkali is added, and methanol is added after completion, and the temperature is cooled to below 10°C by freezing brine, crystallized for 5 hours, centrifuged, dried, discharged, and transferred to the hydrogenation batching kettle. The reaction formula is:

[0019]

[0020] Preferably, in step S2, methanol is added to the batching kettle, and the condensate in the previous step is stirred evenly and then pumped into the hydrogenation kettle, and ammonium salt and catalyst are added, and the air in the kettle is replaced with nitrogen, and the hydrogen pressure in the kettle is controlled to be below 1.5MP, and the temperature does not exceed 30°C to react until the hydrogen pressure in the kettle no longer decreases, and then the temperature is kept at room temperature and pressure for 1-2 hours, and the stirring is turned off, and the feed liquid is allowed to settle for 0.5 hours, and the pressure is released, and the hydrogen in the kettle is replaced with nitrogen twice. The reaction formula is:

[0021]

[0022] Preferably, in the step S3, the methanol in S2 is pumped into a concentration kettle, and the methanol is recovered by atmospheric distillation until the temperature in the kettle reaches 100°C, the vacuum is opened and the distillation is carried out under reduced pressure until there is no distillate, the temperature is lowered to below 40°C, methanol is added, and the mixture is kept warm for crystallization for 1-2 hours, filtered, and the filtrate is atmospheric distilled to recover methanol until the temperature in the kettle reaches 90-100°C, the temperature is lowered to below 60°C, the feed liquid is transferred to a short-path distillation tower, and the distilled liquid is a crude 2-aminoglycerol product, which is transferred to a recrystallization kettle.

[0023] Preferably, in step S4, the crude 2-aminoglycerol in step S3 is drawn into the recrystallization kettle, isopropanol is added, the mixture is stirred and heated until the solution is clear, the temperature is lowered to 0-5°C for crystallization for 2-3 hours, and the mixture is centrifuged and dried to obtain wet 2-aminoglycerol.

[0024] Preferably, in step S5, the 2-aminoglycerol wet material in step S4 is put into a double-cone vacuum dryer, the vacuum valve is opened, the vacuum degree is controlled to be below -0.095 MPa, the temperature is below 60°C, and the material is dried for 15-20 hours, and the material is discharged and packaged at 25 kg / bag to obtain a 2-aminoglycerol finished product.

[0025] (III) Beneficial effects

[0026] Compared with the prior art, the present invention provides a method for preparing 2-aminoglycerol, which has the following characteristics:

[0027] Beneficial effects:

[0028] 1. The preparation method of 2-aminoglycerol uses orthogonal design, single factor test and other means, uses nitromethane and polyformaldehyde as raw materials, effective solvent as medium, adopts metal catalyst with inorganic substance as carrier, uses hydrogen as reducing agent to prepare serinol, and adopts high vacuum distillation for purification, and determines various parameters such as the ratio of various raw materials, reaction temperature, insulation time, crystallization time, hydrogen pressure, vacuum degree, etc. in the whole process. It is further optimized on the basis of the small-scale test process of 2-aminoglycerol, optimizes the hydrogenation reaction conditions, reduces the steps of salt formation process, and increases the yield of 2-aminoglycerol to 80%. The product quality meets the quality requirements of export, has no obvious amplification effect, has simple equipment requirements, and has safe and stable product quality. It can be mass-produced in due time for further promotion and application.

[0029] 2. The preparation method of 2-aminoglycerol further optimizes the process, optimizes the hydrogenation reaction conditions, reduces the salt-forming process steps, and increases the yield of 2-aminoglycerol from 65% of other companies to 80%. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] In order to more clearly illustrate the technical solutions in the embodiments of the present invention, the following briefly introduces the drawings required for describing the embodiments. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative labor:

[0031] Figure 1 It is a schematic diagram of the process flow of the present invention. DETAILED DESCRIPTION

[0032] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. 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.

[0033] Embodiment 1:

[0034] A method for preparing 2-aminoglycerol comprises the following steps:

[0035] S1. Condensation process

[0036] Add drinking water paraformaldehyde, negative methane and alkali solution into the reactor for condensation reaction, then add alkali solution and methanol to generate crystals, add methanol again after centrifugation, centrifuge and dry, then transfer to the hydrogenation batching kettle;

[0037] S2. Hydrogenation process

[0038] Methanol and ammonium salt are added to the hydrogenation batching kettle, and then a catalyst and hydrogen are added to the hydrogenation batching kettle for hydrogenation reaction, and the hydrogen in the hydrogenation batching kettle is replaced with nitrogen. After the hydrogenation reaction is completed, nitrogen is added to perform a second replacement of the hydrogen in the hydrogenation batching kettle;

[0039] S3. Distillation process

[0040] The hydrogenation reaction liquid after substitution is pumped into a concentration kettle, the methanol in the concentration kettle is recovered by distillation at room temperature, isopropanol is added to the concentration kettle for filtration, and the reaction is performed to obtain a crude 2-aminoglycerol product;

[0041] S4, Refining process

[0042] Add isopropanol into the recrystallization kettle, stir, and centrifuge to obtain 2-aminoglycerol wet material;

[0043] S5. Drying process

[0044] The wet 2-aminoglycerol material is put into a double cone vacuum dryer for vacuum drying to obtain a finished 2-aminoglycerol product;

[0045] In step S1, drinking water and paraformaldehyde are added to the reactor, stirring is started, nitromethane is added, cooling water is turned on to cool to 25°C, a small amount of liquid alkali is added to the reactor, and the reaction is kept warm for 6-8 hours, the temperature is controlled below 25°C, liquid alkali is added, methanol is added, and frozen brine is turned on to cool to below 10°C, crystallization is carried out for 5 hours, centrifugation is performed, drying is performed, discharging, and transferring to a hydrogenation batching kettle. The reaction formula is:

[0046]

[0047] In step S2, methanol and the condensate from the previous step are added to the batching kettle, stirred evenly and then pumped into the hydrogenation kettle, and ammonium salt and catalyst are added. The air in the kettle is replaced with nitrogen, and the hydrogen pressure in the kettle is controlled to be below 1.5MP, and the temperature does not exceed 30°C to react until the hydrogen pressure in the kettle no longer decreases, and then the temperature is kept at room temperature and pressure for 1-2 hours, the stirring is turned off, the feed liquid is allowed to settle for 0.5 hours, the pressure is released, and the hydrogen in the kettle is replaced with nitrogen twice. The reaction formula is:

[0048]

[0049] In step S3, the product in S2 is pumped into a concentration kettle, and the methanol is recovered by atmospheric distillation until the temperature in the kettle reaches 100°C, the vacuum is opened and the distillation is carried out under reduced pressure until there is no distillate, the temperature is lowered to below 40°C, methanol is added, and the product is kept warm for crystallization for 1-2 hours, filtered, and the filtrate is atmospheric distilled to recover methanol until the temperature in the kettle reaches 90-100°C, the temperature is lowered to below 60°C, the feed liquid is transferred to a short-path distillation tower, and the distilled liquid is a crude 2-aminoglycerol product, which is transferred to a recrystallization kettle.

[0050] In step S4, the crude 2-aminoglycerol product in step S3 is drawn into a recrystallization kettle, isopropanol is added, the mixture is stirred and heated until the solution is clear, the temperature is lowered to 0-5° C. for crystallization for 2-3 hours, and the mixture is centrifuged and dried to obtain wet 2-aminoglycerol.

[0051] In step S5, the 2-aminoglycerol wet material in step S4 is put into a double-cone vacuum dryer, the vacuum valve is opened, the vacuum degree is controlled to be below -0.095 MPa, the temperature is below 60° C. and dried for 15-20 hours, the material is discharged and packaged at 25 kg / bag to obtain a 2-aminoglycerol finished product.

[0052] Using orthogonal design, single factor test and other means, nitromethane and polyformaldehyde are used as raw materials, effective solvents are used as media, metal catalysts with inorganic materials as carriers, and hydrogen as reducing agent to prepare serinol, and high vacuum distillation is used for purification, and various parameters such as the ratio of various raw materials, reaction temperature, insulation time, crystallization time, hydrogen pressure, vacuum degree, etc. in the whole process are determined. Further optimization is carried out on the basis of the small-scale test process of 2-aminoglycerol, the hydrogenation reaction conditions are optimized, the steps of the salt-forming process are reduced, and the yield of 2-aminoglycerol is increased to 80%. The product quality meets the quality requirements for export, there is no obvious amplification effect, the equipment requirements are simple, the product quality is safe and stable, and large-scale production can be carried out in a timely manner for further promotion and application.

[0053] Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A method for preparing 2-aminoglycerol, characterized in that: The following steps are involved: S1. Condensation process Add drinking water paraformaldehyde, negative methane and alkali solution into the reactor for condensation reaction, then add alkali solution and methanol to generate crystals, add methanol again after centrifugation, centrifuge and dry, then transfer to the hydrogenation batching kettle; S2. Hydrogenation process Methanol and ammonium salt are added to the hydrogenation batching kettle, and then a catalyst and hydrogen are added to the hydrogenation batching kettle for hydrogenation reaction, and the hydrogen in the hydrogenation batching kettle is replaced with nitrogen. After the hydrogenation reaction is completed, nitrogen is added to perform a second replacement of the hydrogen in the hydrogenation batching kettle; S3. Distillation process The hydrogenation reaction liquid after substitution is pumped into a concentration kettle, the methanol in the concentration kettle is recovered by distillation at room temperature, isopropanol is added to the concentration kettle for filtration, and the reaction is performed to obtain a crude 2-aminoglycerol product; S4, Refining process Add isopropanol into the recrystallization kettle, stir, and centrifuge to obtain 2-aminoglycerol wet material; S5. Drying process The wet 2-aminoglycerol material is put into a double-cone vacuum dryer for vacuum drying to obtain a finished 2-aminoglycerol product.

2. The method for preparing 2-aminoglycerol according to claim 1, characterized in that: In the step S1, drinking water and paraformaldehyde are added to the reactor, stirring is started, nitromethane is added, cooling water is turned on to cool to 25°C, a small amount of liquid alkali is added to the reactor, and the reaction is kept warm for 6-8 hours, the temperature is controlled below 25°C, liquid alkali is added, methanol is added, and the temperature is cooled to below 10°C with frozen brine, crystallized for 5 hours, centrifuged, dried, discharged, and transferred to the hydrogenation batching kettle. The reaction formula is:

3. The method for preparing 2-aminoglycerol according to claim 1, characterized in that: In the step S2, methanol is added to the batching kettle, and the condensate of the previous step is stirred evenly and then pumped into the hydrogenation kettle, and ammonium salt and catalyst are added, and the air in the kettle is replaced with nitrogen, and the hydrogen pressure in the kettle is controlled to be below 1.5MP, and the temperature does not exceed 30°C to react until the hydrogen pressure in the kettle no longer decreases, and then the temperature is kept at room temperature and pressure for 1-2 hours, and the stirring is turned off, and the feed liquid is allowed to settle for 0.5 hours, and the pressure is released, and the hydrogen in the kettle is replaced with nitrogen twice. The reaction formula is:

4. The method for preparing 2-aminoglycerol according to claim 1, characterized in that: In the step S3, the methanol in S2 is pumped into a concentration kettle, and the methanol is recovered by atmospheric distillation until the temperature in the kettle reaches 100°C, the vacuum is opened and the distillation is carried out under reduced pressure until there is no distillate, the temperature is lowered to below 40°C, methanol is added, and the mixture is kept warm for crystallization for 1-2 hours, filtered, and the filtrate is atmospheric distilled to recover methanol until the temperature in the kettle reaches 90-100°C, the temperature is lowered to below 60°C, the feed liquid is transferred to a short-path distillation tower, and the distilled liquid is a crude 2-aminoglycerol product, which is transferred to a recrystallization kettle.

5. The method for preparing 2-aminoglycerol according to claim 1, characterized in that: In the step S4, the crude 2-aminoglycerol in the step S3 is drawn into the recrystallization kettle, isopropanol is added, the mixture is stirred and heated until the solution is clear, the temperature is lowered to 0-5°C for crystallization for 2-3 hours, and the mixture is centrifuged and dried to obtain wet 2-aminoglycerol.

6. The method for preparing 2-aminoglycerol according to claim 1, characterized in that: In the step S5, the 2-aminoglycerol wet material in the step S4 is put into a double-cone vacuum dryer, the vacuum valve is opened, the vacuum degree is controlled to be below -0.095 MPa, the temperature is below 60° C. and dried for 15-20 hours, the material is discharged, and packaged at 25 kg / bag to obtain a 2-aminoglycerol finished product.

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