Preparation method of bis (2-ethoxyl) amino (trihydroxymethyl) methane

Abstract

The invention relates to a preparation method of bis (2-ethoxyl) amino (trihydroxymethyl) methane, which comprises the following step: reacting tris (hydroxymethyl) aminomethane with ethylene oxide at 10-40 DEG C to obtain the bis (2-ethoxyl) amino (trihydroxymethyl) methane. According to the preparation method of the bis (2-ethoxyl) amino (trihydroxymethyl) methane, provided by the invention, the reaction raw materials are simple, economical and environment-friendly; reaction conditions are mild, reaction can be carried out at room temperature, energy consumption is low, and side reactions are few; the preparation process is simple to operate, and has higher yield and purity.

Description

Technical Field

[0001] The invention relates to the technical field of organic synthesis, and in particular to a method for preparing bis(2-hydroxyethyl)amino(trihydroxymethyl)methane. Background Art

[0002] As a synthetic buffer, bis(2-hydroxyethyl)amino(trihydroxymethyl)methane has good acid-base adjustment ability and a wide pH adjustment range, which can adapt to a variety of experimental conditions, especially in biochemical experiments that are sensitive to pH. Bis(2-hydroxyethyl)amino(trihydroxymethyl)methane is often used to detect creatine creatine enzyme and creatine phosphokinase. With the change of temperature, its dissociation constant changes only slightly. Its effective pH buffer range is 5.8-7.2, which is suitable for the separation of hemoglobin.

[0003] All-iron flow battery is a new type of energy storage technology that uses iron as an active material and has the characteristics of low cost and environmental friendliness. In all-iron flow batteries, the use of complexing agents is to enhance the stability of iron ions in solution and battery performance. Bis(2-hydroxyethyl)amino(trihydroxymethyl)methane (Bis-Tris) is a complexing agent that may be used in all-iron flow batteries. In the field of all-iron flow batteries, the Fe / Fe ratio is improved by introducing complexing agents and polar solvents. 2+ The reversibility of the deposition-dissolution reaction and the inhibition of hydrogen evolution enable efficient, stable and long-cycle operation of the battery. In addition, the complexing agent is used in the negative electrode electrolyte of the alkaline all-iron liquid flow battery, which enables the electrolyte to avoid the precipitation of iron element during the charge and discharge process and effectively prevents the formation of iron hydroxide precipitation, thereby improving the stability of iron ions and extending the cycle life of the electrolyte. Therefore, Bis-Tris may play an important role as a complexing agent in all-iron liquid flow batteries, helping to improve battery performance and stability, and research on its preparation method is conducive to promoting its widespread application.

[0004] Patent CN101402576A discloses a method for preparing di(2-hydroxyethyl)iminotri(hydroxymethyl)methane, which uses tris(hydroxymethyl)aminomethane and chloroethanol as raw materials, reacts in an aqueous solution, and adds alkali at room temperature to synthesize at 60°C. However, chloroethanol is highly toxic, the reaction operation process is complicated, the reaction time is long, and sodium chloride is produced as a byproduct, which causes equipment corrosion and is not clean and environmentally friendly.

[0005] Patent CN101659621A discloses a method for preparing bis(2-hydroxyethyl)amino(trihydroxymethyl)methane, which discloses using anionic resin as a catalyst, ethylene carbonate and tris(hydroxymethyl)aminomethane as starting materials, and performing a reaction at a temperature of 60-100° C. for 20-48 hours. The reaction temperature is relatively high and the yield is relatively low.

[0006] Patent CN103467312A discloses a method for preparing Bis-Tris. The patent discloses that Bis-Tris is synthesized by passing gaseous ethylene oxide into a liquid aqueous solution to form a saturated ethylene oxide solution. Sodium bisulfite is introduced into the reaction, and by-products such as sodium sulfite are generated. The product is not easy to purify and the yield is low.

[0007] Therefore, it is of great significance to provide a method for preparing bis(2-hydroxyethyl)amino(trihydroxymethyl)methane with mild reaction conditions, simple operation, few reaction by-products, economical raw materials and environmental friendliness. Summary of the invention

[0008] In order to solve the above technical problems, the present invention provides a method for preparing bis(2-hydroxyethyl)amino(trihydroxymethyl)methane. The preparation method uses an aqueous solution of tris(hydroxymethyl)aminomethane and ethylene oxide as raw materials and reacts at room temperature to obtain the product. The preparation method is simple, the reaction conditions are mild, the reaction by-products are small, the raw materials are economical and the product is environmentally friendly.

[0009] To achieve this object, the present invention adopts the following technical solutions:

[0010] In a first aspect, the present invention provides a method for preparing bis(2-hydroxyethyl)amino(trihydroxymethyl)methane, the preparation method comprising the following steps:

[0011] Tris(hydroxymethyl)aminomethane and ethylene oxide are reacted at 10-40° C. to obtain the bis(2-hydroxyethyl)amino(trihydroxymethyl)methane.

[0012] The synthetic route of the present invention is as follows:

[0013]

[0014] The reaction temperature of the present invention is 10-40°C, for example, it can be 13°C, 15°C, 20°C, 22°C, 25°C, 28°C, 30°C, 32°C, 35°C or 38°C, and is not limited to the listed values. Other unlisted data within the numerical range are also applicable.

[0015] In the present invention, only tris(hydroxymethyl)aminomethane and ethylene oxide are used as starting materials for the reaction, and no other catalyst or raw materials are added. This reduces the economic cost and avoids the generation of by-products, thereby reducing the difficulty of post-processing. Furthermore, the entire operation process is greatly simplified while ensuring a high yield and purity.

[0016] Compared with the synthesis method of preparing bis(2-hydroxyethyl)amino(trihydroxymethyl)methane using chloroethanol as the starting material in the prior art, the present invention uses ethylene oxide as the starting material, which can not only avoid the corrosion of the experimental equipment by the chlorine element, but also avoid the generation of the byproduct sodium chloride in the entire preparation process. After the reaction is completed, there is no need to carry out a special step of removing impurities from sodium chloride, which greatly simplifies the operation process. In addition, using ethylene oxide to replace highly toxic chloroethanol for the reaction can increase the safety of the reaction; at the same time, the reaction of the present invention can be carried out at 10-40°C, which effectively avoids the temperature limit of 60°C for the reaction temperature condition, which is conducive to reducing energy consumption and thus reducing economic costs.

[0017] Preferably, the concentration of the tris(hydroxymethyl)aminomethane aqueous solution is 5-40%, for example, 8%, 10%, 15%, 20%, 25%, 30%, 32%, 35%, 38% or 40%, but is not limited to the listed values, and other unlisted data within the numerical range are also applicable, and more preferably 10-30%.

[0018] In the present invention, the concentration of the tris(hydroxymethyl)aminomethane aqueous solution is 5-40%. When the concentration is lower than 5%, the reaction rate is slow and the reaction efficiency is low. When the concentration is higher than 40%, a supersaturated solution is formed, so that tris(hydroxymethyl)aminomethane is precipitated in water, which not only affects the yield but also causes a waste of raw materials.

[0019] Preferably, the solvent water in the tris(hydroxymethyl)aminomethane aqueous solution includes any one of purified water, distilled water or deionized water, or a combination of at least two of them.

[0020] Preferably, the molar ratio of tris(hydroxymethyl)aminomethane to ethylene oxide is 1:(2-10), for example, 1:2, 1:2.5, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9 or 1:10, not limited to the listed values, other unlisted data within the numerical range are also applicable, and more preferably 1:(3-6).

[0021] In the present invention, the molar ratio of tris(hydroxymethyl)aminomethane to ethylene oxide is 1:(2-10). When the molar ratio of the two is lower than 1:2, the addition amount of ethylene oxide is too low, so that the tris(hydroxymethyl)aminomethane cannot be completely reacted, thereby reducing the reaction efficiency; when the molar ratio of the two is higher than 1:10, the excessive ethylene oxide will cause side reactions such as self-polymerization, which not only affects the synthesis of bis(2-hydroxyethyl)amino(trihydroxymethyl)methane and thus reduces its yield, but also the generated by-products will increase the difficulty of post-reaction treatment, and also reduce the purity of bis(2-hydroxyethyl)amino(trihydroxymethyl)methane. Further, when the molar ratio of the two is 1:(3-6), the product has a better yield and purity.

[0022] Preferably, the ethylene oxide is added at ≤10°C, for example, it can be -20°C, -15°C, -10°C, -5°C, -3°C, 0°C, 3°C, 5°C, 8°C or 10°C, not limited to the listed values, other unlisted data within the numerical range are also applicable, more preferably -10°C to 10°C.

[0023] In the present invention, ethylene oxide is added at ≤10°C. This is because the boiling point of ethylene oxide is 10.8°C. During the addition process, the temperature of the system is controlled not to be higher than 10°C, which is conducive to adding ethylene oxide in a liquid state. This is not only conducive to mixing it with the tris(hydroxymethyl)aminomethane aqueous solution, thereby helping to improve the reaction efficiency; it also avoids the system being under negative pressure in the subsequent reaction, thereby further improving the safety of the reaction.

[0024] Preferably, the ethylene oxide needs to be replaced with a protective gas before being added.

[0025] In the present invention, before the addition of ethylene oxide, gas replacement is performed 2-3 times with protective gas so as to replace the air in the reaction system with protective gas, thereby reducing the flammable and explosive risks of ethylene oxide. At the same time, the reaction is carried out at room temperature, and ethylene oxide is in gaseous state, which is conducive to forming a slightly positive pressure environment in the reaction system, further improving the safety of the reaction.

[0026] Preferably, the protective gas comprises an inert gas.

[0027] Preferably, the inert gas includes any one of nitrogen, argon or helium, or a combination of at least two of them.

[0028] Preferably, the reaction time is 12-24 h, for example, 13 h, 14 h, 15 h, 16 h, 17 h, 18 h, 19 h, 20 h, 21 h or 23 h, and is not limited to the listed values. Other unlisted data within the numerical range are also applicable.

[0029] The invention reduces the reaction time and further improves the reaction efficiency by specifically selecting the raw materials and optimizing the reaction conditions.

[0030] Preferably, the reaction further includes a post-treatment process after completion.

[0031] Preferably, the post-treatment process includes concentration, recrystallization and drying.

[0032] Preferably, the concentration comprises reduced pressure concentration and / or freeze-drying concentration.

[0033] Preferably, the recrystallization is to dissolve the concentrated crude product with an alcohol solvent and crystallize it by cooling.

[0034] Preferably, the alcohol solvent includes any one of methanol, ethanol, propanol, isopropanol, n-butanol, n-pentanol, cyclopentanol or cyclohexanol, or a combination of at least two thereof.

[0035] Preferably, the mass of the alcohol solvent is 0.5-5 times the mass of the crude product, for example, it can be 0.8 times, 1 times, 1.5 times, 2 times, 2.5 times, 3 times, 3.5 times, 4 times, 4.5 times or 4.8 times, not limited to the listed values, and other unlisted data within the numerical range are also applicable, and further preferably 1-3 times.

[0036] Preferably, the drying comprises any one of rotary evaporation drying, freeze drying, nitrogen drying or atmospheric pressure drying, or a combination of at least two thereof.

[0037] Preferably, the recrystallization is filtered, washed and then dried.

[0038] Preferably, the filtration comprises vacuum filtration and / or centrifugal filtration.

[0039] Preferably, the washing detergent comprises any one of methanol, ethanol, propanol, isopropanol, n-butanol, n-pentanol, cyclopentanol or cyclohexanol, or a combination of at least two thereof.

[0040] Preferably, the preparation method specifically comprises the following steps:

[0041] A 5-40% tris(hydroxymethyl)aminomethane aqueous solution is replaced with a protective gas, and ethylene oxide is added at ≤10°C to make a molar ratio of tris(hydroxymethyl)aminomethane to ethylene oxide of 1:(2-10). After the addition of ethylene oxide is completed, the temperature is raised to 10-40°C for reaction for 12-24 hours. After the reaction is completed, the reaction solution is concentrated to obtain a crude product, which is recrystallized and dried using an alcohol solvent to obtain the bis(2-hydroxyethyl)amino(trihydroxymethyl)methane.

[0042] Compared with the prior art, the present invention has at least the following beneficial effects:

[0043] The preparation method of bis(2-hydroxyethyl)amino(trihydroxymethyl)methane provided by the present invention has simple reaction raw materials, few side reactions, mild reaction conditions, can react at room temperature, has low cost and is environmentally friendly. The yield of bis(2-hydroxyethyl)amino(trihydroxymethyl)methane of the obtained product can reach 80.9% and the purity can reach 99.3%. BRIEF DESCRIPTION OF THE DRAWINGS

[0044] Figure 1 is the hydrogen nuclear magnetic resonance spectrum of the product obtained in Example 1;

[0045] Figure 2 It is the carbon NMR spectrum of the product obtained in Example 1. DETAILED DESCRIPTION

[0046] The technical solution of the present invention is further described below in conjunction with the accompanying drawings and through specific implementation methods. However, the following examples are only simplified examples of the present invention and do not represent or limit the scope of protection of the present invention. The scope of protection of the present invention shall be subject to the claims.

[0047] Example 1

[0048] In a 500mL three-necked flask, add 28g tris(hydroxymethyl)aminomethane and 252g purified water to prepare a 10% tris(hydroxymethyl)aminomethane aqueous solution, pass nitrogen into the three-necked flask for gas replacement three times, and pass 30.54g ethylene oxide into the three-necked flask at -10°C to make the molar ratio of tris(hydroxymethyl)aminomethane to ethylene oxide 1:3, and control the temperature below 10°C. After the ethylene oxide is passed, heat to 20°C and react for 23h. After the reaction is completed, the reaction solution is concentrated under reduced pressure to obtain a crude product. Then add 2 times the weight of anhydrous ethanol, shake well, cool and crystallize, and after reduced pressure filtration, the solid is washed with anhydrous ethanol and dried at normal pressure to obtain white crystals of bis(2-hydroxyethyl)amino(trihydroxymethyl)methane.

[0049] The NMR characterization data of the bis(2-hydroxyethyl)amino(trihydroxymethyl)methane are as follows:

[0050] 1 H NMR (300MHz, D2O): δ3.552-3.505(s,6H),3.485-3.464(t,4H),2.861-2.841(t,4H);

[0051] 13 C NMR (300MHz, D2O): δ63.802, 61.135, 60.747, 51.224.

[0052] The melting point of the sample obtained by the reaction was tested and the melting point was measured to be 103-104°C, which was consistent with the melting point of the standard sample.

[0053] like Figure 1 As shown, δ=4.692 is the absorption peak of D2O solvent, δ=2.841-2.861 is the four hydrogen atoms of -N(CH2)2, δ=3.464-3.485 is the four hydrogen atoms of (CH2CH2OH)2, and δ=3.505-3.552 is the six hydrogen atoms of C(CH2OH)3.

[0054] like Figure 2As shown, δ=51.224 represents the two carbon atoms of -N(CH2)2, δ=60.747 represents the two carbon atoms of (CH2CH2OH)2, δ=61.135 represents the three carbon atoms of C(CH2OH)3, and δ=63.802 represents the one carbon atom of C(CH2OH)3, which is consistent with the standard spectrum of bis(2-hydroxyethyl)amino(trihydroxymethyl)methane.

[0055] Example 2

[0056] In a 500mL three-necked flask, add 28g tris(hydroxymethyl)aminomethane and 158.67g purified water to make a 15% tris(hydroxymethyl)aminomethane aqueous solution, pass nitrogen into the three-necked flask for gas replacement three times, and pass 40.73g ethylene oxide into the three-necked flask at -10°C to make the molar ratio of tris(hydroxymethyl)aminomethane to ethylene oxide 1:4, and control the temperature below 10°C. After the ethylene oxide is passed, heat to 25°C and react for 22h. After the reaction is completed, the reaction solution is concentrated under reduced pressure to obtain a crude product. Then add 1.5 times the weight of anhydrous ethanol, shake well, cool and crystallize, and after reduced pressure filtration, the solid is washed with anhydrous ethanol and dried at normal pressure to obtain white crystals of bis(2-hydroxyethyl)amino(trihydroxymethyl)methane.

[0057] Example 3

[0058] In a 500mL three-necked flask, add 28g tris(hydroxymethyl)aminomethane and 112g purified water to prepare a 20% tris(hydroxymethyl)aminomethane aqueous solution, pass nitrogen into the three-necked flask for gas replacement three times, and pass 50.91g ethylene oxide into the three-necked flask at -10°C to make the molar ratio of tris(hydroxymethyl)aminomethane to ethylene oxide 1:5, and control the temperature below 10°C. After the ethylene oxide is passed, heat to 30°C and react for 20h. After the reaction is completed, the reaction solution is concentrated under reduced pressure to obtain a crude product. Then add 3 times the weight of anhydrous ethanol, shake well, cool and crystallize, and after reduced pressure filtration, the solid is washed with anhydrous ethanol and dried at normal pressure to obtain white crystals of bis(2-hydroxyethyl)amino(trihydroxymethyl)methane.

[0059] Example 4

[0060] In a 1000mL three-necked flask, add 28g tris(hydroxymethyl)aminomethane and 532g purified water to prepare a 5% tris(hydroxymethyl)aminomethane aqueous solution, pass nitrogen into the three-necked flask for gas replacement three times, and pass 20.34g ethylene oxide into the three-necked flask at 10°C to make the molar ratio of tris(hydroxymethyl)aminomethane to ethylene oxide 1:2, and control the temperature below 10°C. After the ethylene oxide is passed, heat to 10°C and react for 24h. After the reaction is completed, the reaction solution is concentrated under reduced pressure to obtain a crude product. Then add 0.5 times the weight of isopropanol, shake well, cool and crystallize, and after reduced pressure filtration, the solid is washed with isopropanol and dried at normal pressure to obtain white crystals of bis(2-hydroxyethyl)amino(trihydroxymethyl)methane.

[0061] Example 5

[0062] In a 500mL three-necked flask, add 28g tris(hydroxymethyl)aminomethane and 42g purified water to prepare a 40% tris(hydroxymethyl)aminomethane aqueous solution, pass nitrogen into the three-necked flask for gas replacement three times, and pass 101.76g ethylene oxide into the three-necked flask at 0°C, so that the molar ratio of tris(hydroxymethyl)aminomethane to ethylene oxide is 1:10, and the temperature is controlled below 10°C. After the ethylene oxide is passed, the temperature is raised to 40°C and the reaction is carried out for 12 hours. After the reaction is completed, the reaction solution is concentrated under reduced pressure to obtain a crude product. Then, 5 times the weight of n-butanol is added, shaken well, and cooled to crystallize. After reduced pressure filtration, the solid is washed with n-butanol and dried by rotary evaporation to obtain white crystals of bis(2-hydroxyethyl)amino(trihydroxymethyl)methane.

[0063] Example 6

[0064] In a 1000mL three-necked flask, add 28g tris(hydroxymethyl)aminomethane and 532g purified water to prepare a 5% tris(hydroxymethyl)aminomethane aqueous solution, pass nitrogen into the three-necked flask for gas replacement three times, and pass 50.91g ethylene oxide into the three-necked flask at -10°C to make the molar ratio of tris(hydroxymethyl)aminomethane to ethylene oxide 1:5, and control the temperature below 10°C. After the ethylene oxide is passed, heat to 30°C and react for 20h. After the reaction is completed, the reaction solution is concentrated under reduced pressure to obtain a crude product. Then add 3 times the weight of anhydrous ethanol, shake well, cool and crystallize, and after reduced pressure filtration, the solid is washed with anhydrous ethanol and dried at normal pressure to obtain white crystals of bis(2-hydroxyethyl)amino(trihydroxymethyl)methane.

[0065] Example 7

[0066] In a 500mL three-necked flask, add 28g tris(hydroxymethyl)aminomethane and 252g purified water to prepare a 10% tris(hydroxymethyl)aminomethane aqueous solution, pass nitrogen into the three-necked flask for gas replacement three times, and pass 50.91g ethylene oxide into the three-necked flask at -10°C to make the molar ratio of tris(hydroxymethyl)aminomethane to ethylene oxide 1:5, and control the temperature below 10°C. After the ethylene oxide is passed, heat to 30°C and react for 20h. After the reaction is completed, the reaction solution is concentrated under reduced pressure to obtain a crude product. Then add 3 times the weight of anhydrous ethanol, shake well, cool and crystallize, and after reduced pressure filtration, the solid is washed with anhydrous ethanol and dried at normal pressure to obtain white crystals of bis(2-hydroxyethyl)amino(trihydroxymethyl)methane.

[0067] Example 8

[0068] In a 500mL three-necked flask, add 28g tris(hydroxymethyl)aminomethane and 65g purified water to prepare a 30% tris(hydroxymethyl)aminomethane aqueous solution, pass nitrogen into the three-necked flask for gas replacement three times, and pass 50.91g ethylene oxide into the three-necked flask at -10°C to make the molar ratio of tris(hydroxymethyl)aminomethane to ethylene oxide 1:5, and control the temperature below 10°C. After the ethylene oxide is passed, heat to 30°C and react for 20h. After the reaction is completed, the reaction solution is concentrated under reduced pressure to obtain a crude product. Then add 3 times the weight of anhydrous ethanol, shake well, cool and crystallize, and after reduced pressure filtration, the solid is washed with anhydrous ethanol and dried at normal pressure to obtain white crystals of bis(2-hydroxyethyl)amino(trihydroxymethyl)methane.

[0069] Example 9

[0070] In a 500mL three-necked flask, add 28g tris(hydroxymethyl)aminomethane and 52g purified water to prepare a 35% tris(hydroxymethyl)aminomethane aqueous solution, pass nitrogen into the three-necked flask for gas replacement three times, and pass 50.91g ethylene oxide into the three-necked flask at -10°C to make the molar ratio of tris(hydroxymethyl)aminomethane to ethylene oxide 1:5, and control the temperature below 10°C. After the ethylene oxide is passed, heat to 30°C and react for 20h. After the reaction is completed, the reaction solution is concentrated under reduced pressure to obtain a crude product. Then add 3 times the weight of anhydrous ethanol, shake well, cool and crystallize, and after reduced pressure filtration, the solid is washed with anhydrous ethanol and dried at normal pressure to obtain white crystals of bis(2-hydroxyethyl)amino(trihydroxymethyl)methane.

[0071] Example 10

[0072] In a 500mL three-necked flask, add 28g tris(hydroxymethyl)aminomethane and 112g purified water to prepare a 20% tris(hydroxymethyl)aminomethane aqueous solution, pass nitrogen into the three-necked flask for gas replacement three times, and pass 20.34g ethylene oxide into the three-necked flask at -10°C to make the molar ratio of tris(hydroxymethyl)aminomethane to ethylene oxide 1:2, and control the temperature below 10°C. After the ethylene oxide is passed, heat to 30°C and react for 20h. After the reaction is completed, the reaction solution is concentrated under reduced pressure to obtain a crude product. Then add 3 times the weight of anhydrous ethanol, shake well, cool and crystallize, and after reduced pressure filtration, the solid is washed with anhydrous ethanol and dried at normal pressure to obtain white crystals of bis(2-hydroxyethyl)amino(trihydroxymethyl)methane.

[0073] Embodiment 11

[0074] In a 500mL three-necked flask, add 28g tris(hydroxymethyl)aminomethane and 112g purified water to prepare a 20% tris(hydroxymethyl)aminomethane aqueous solution, pass nitrogen into the three-necked flask for gas replacement three times, and pass 30.54g ethylene oxide into the three-necked flask at -10°C to make the molar ratio of tris(hydroxymethyl)aminomethane to ethylene oxide 1:3, and control the temperature below 10°C. After the ethylene oxide is passed, heat to 30°C and react for 20h. After the reaction is completed, the reaction solution is concentrated under reduced pressure to obtain a crude product. Then add 3 times the weight of anhydrous ethanol, shake well, cool and crystallize, and after reduced pressure filtration, the solid is washed with anhydrous ethanol and dried at normal pressure to obtain white crystals of bis(2-hydroxyethyl)amino(trihydroxymethyl)methane.

[0075] Example 12

[0076] In a 500mL three-necked flask, add 28g tris(hydroxymethyl)aminomethane and 112g purified water to prepare a 20% tris(hydroxymethyl)aminomethane aqueous solution, pass nitrogen into the three-necked flask for gas replacement three times, and pass 61.06g ethylene oxide into the three-necked flask at -10°C to make the molar ratio of tris(hydroxymethyl)aminomethane to ethylene oxide 1:6, and control the temperature below 10°C. After the ethylene oxide is passed, heat to 30°C and react for 20h. After the reaction is completed, the reaction solution is concentrated under reduced pressure to obtain a crude product. Then add 3 times the weight of anhydrous ethanol, shake well, cool and crystallize, and after reduced pressure filtration, the solid is washed with anhydrous ethanol and dried at normal pressure to obtain white crystals of bis(2-hydroxyethyl)amino(trihydroxymethyl)methane.

[0077] Embodiment 13

[0078] In a 500mL three-necked flask, add 28g tris(hydroxymethyl)aminomethane and 112g purified water to prepare a 20% tris(hydroxymethyl)aminomethane aqueous solution, pass nitrogen into the three-necked flask for gas replacement three times, and pass 71.27g ethylene oxide into the three-necked flask at -10°C to make the molar ratio of tris(hydroxymethyl)aminomethane to ethylene oxide 1:7, and control the temperature below 10°C. After the ethylene oxide is passed, heat to 30°C and react for 20h. After the reaction is completed, the reaction solution is concentrated under reduced pressure to obtain a crude product. Then add 3 times the weight of anhydrous ethanol, shake well, cool and crystallize, and after reduced pressure filtration, the solid is washed with anhydrous ethanol and dried at normal pressure to obtain white crystals of bis(2-hydroxyethyl)amino(trihydroxymethyl)methane.

[0079] The yield and purity of bis(2-hydroxyethyl)amino(trihydroxymethyl)methane obtained in the above Examples 1-13 are shown in Table 1.

[0080] Table 1

[0081]

[0082]

[0083] The test results show that:

[0084] (1) It can be seen from Examples 1 to 13 that the present invention uses tris(hydroxymethyl)aminomethane and ethylene oxide as starting materials to react at room temperature to prepare the product bis(2-hydroxyethyl)amino(trihydroxymethyl)methane in a yield of 57.8-80.9% and a purity of 97.5-99.3%.

[0085] (2) By comparing Example 3 with Examples 6-9, it can be seen that in the preparation method of the present invention, the concentration of the starting material tris(hydroxymethyl)aminomethane aqueous solution will affect the yield of the product. When its concentration is 10-30%, the yield is better. When its concentration is lower than 10% or higher than 30%, its yield will decrease.

[0086] (3) It can be seen from Examples 3 and 10-13 that in the preparation method of the present invention, when the molar ratio of tris(hydroxymethyl)aminomethane to ethylene oxide is 1:(3-6), the yield and purity are better. When the molar ratio of the two is lower than 1:3, the yield decreases; when the molar ratio of the two is higher than 1:6, the yield and purity are both reduced.

[0087] The applicant declares that the above is only a specific implementation mode of the present invention, but the protection scope of the present invention is not limited thereto. Those skilled in the art should understand that any changes or substitutions that can be easily thought of by those skilled in the art within the technical scope disclosed by the present invention shall fall within the protection scope and disclosure scope of the present invention.

Claims

1. A method for preparing bis(2-hydroxyethyl)amino(trihydroxymethyl)methane, characterized in that: The preparation method comprises the following steps: Tris(hydroxymethyl)aminomethane and ethylene oxide are reacted at 10-40° C. to obtain the bis(2-hydroxyethyl)amino(trihydroxymethyl)methane.

2. The method for preparing bis(2-hydroxyethyl)amino(trihydroxymethyl)methane according to claim 1, characterized in that: The tris(hydroxymethyl)aminomethane is a tris(hydroxymethyl)aminomethane aqueous solution; Preferably, the concentration of the tris(hydroxymethyl)aminomethane aqueous solution is 5-40%, preferably 10-30%; Preferably, the solvent water in the tris(hydroxymethyl)aminomethane aqueous solution includes any one of purified water, distilled water or deionized water, or a combination of at least two of them.

3. The method for preparing bis(2-hydroxyethyl)amino(trihydroxymethyl)methane according to claim 1 or 2, characterized in that: The molar ratio of tris(hydroxymethyl)aminomethane to ethylene oxide is 1:(2-10), preferably 1:(3-6).

4. The method for preparing bis(2-hydroxyethyl)amino(trihydroxymethyl)methane according to any one of claims 1 to 3, characterized in that: The ethylene oxide is added at ≤10°C, preferably -10°C to 10°C.

5. The method for preparing bis(2-hydroxyethyl)amino(trihydroxymethyl)methane according to any one of claims 1 to 4, characterized in that: The ethylene oxide needs to be replaced with a protective gas before being added; Preferably, the protective gas comprises an inert gas; Preferably, the inert gas includes any one of nitrogen, argon or helium, or a combination of at least two of them.

6. The method for preparing bis(2-hydroxyethyl)amino(trihydroxymethyl)methane according to any one of claims 1 to 5, characterized in that: The reaction time is 12-24h.

7. The method for preparing bis(2-hydroxyethyl)amino(trihydroxymethyl)methane according to any one of claims 1 to 6, characterized in that: The reaction further includes a post-treatment process after completion.

8. The method for preparing bis(2-hydroxyethyl)amino(trihydroxymethyl)methane according to claim 7, characterized in that: The post-treatment process includes concentration, recrystallization and drying; Preferably, the concentration comprises reduced pressure concentration and / or freeze-drying concentration; Preferably, the recrystallization is to dissolve the concentrated crude product with an alcohol solvent and crystallize it by cooling; The alcohol solvent includes any one of methanol, ethanol, propanol, isopropanol, n-butanol, n-pentanol, cyclopentanol or cyclohexanol, or a combination of at least two thereof; Preferably, the mass of the alcohol solvent is 0.5-5 times, preferably 1-3 times, the mass of the crude product; Preferably, the drying comprises any one of rotary evaporation drying, freeze drying, nitrogen drying or atmospheric pressure drying, or a combination of at least two thereof.

9. The method for preparing bis(2-hydroxyethyl)amino(trihydroxymethyl)methane according to claim 8, characterized in that: After the recrystallization, the process needs to be filtered, washed and then dried; Preferably, the filtration comprises vacuum filtration and / or centrifugal filtration; Preferably, the washing detergent comprises any one of methanol, ethanol, propanol, isopropanol, n-butanol, n-pentanol, cyclopentanol or cyclohexanol, or a combination of at least two thereof.

10. The method for preparing bis(2-hydroxyethyl)amino(trihydroxymethyl)methane according to any one of claims 1 to 9, characterized in that: The preparation method specifically comprises the following steps: A 5-40% tris(hydroxymethyl)aminomethane aqueous solution is replaced with a protective gas, and ethylene oxide is added at ≤10°C to make a molar ratio of tris(hydroxymethyl)aminomethane to ethylene oxide of 1:(2-10). After the addition of ethylene oxide is completed, the temperature is raised to 10-40°C for reaction for 12-24 hours. After the reaction is completed, the reaction solution is concentrated to obtain a crude product, which is recrystallized and dried using an alcohol solvent to obtain the bis(2-hydroxyethyl)amino(trihydroxymethyl)methane.

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