CN120736999A - Synthesis, separation and purification method of N-alkyl-beta-aminopropionate - Google Patents

Abstract

The invention discloses a method for synthesizing, separating and purifying N-alkyl-beta-amino propionate, belonging to the technical field of organic synthesis. Sequentially carrying out addition reaction and saponification reaction on long-chain fatty amine and an acrylic ester compound to obtain a saponification reaction liquid, regulating the temperature of the saponification reaction liquid to 55-70 ℃, simultaneously adding water and regulating the pH value to 3.0-5.0 by adopting acid liquor, fully stirring, standing for layering, separating an upper organic layer by hot liquid separation, continuously regulating the pH value of the organic layer to 0.5-1.5 by adopting acid liquor, cooling to realize layering, and separating an upper product to be neutralized by adopting alkali solution to obtain the N-alkyl-beta-aminopropionate. The method has the advantages of simple operation, short flow, high product separation recovery rate and high purity, can reduce the production cost of the N-alkyl-beta-sodium aminopropionate, and meets the industrial production.

Description

Synthesis, separation and purification method of N-alkyl-beta-aminopropionate

Technical Field

The invention relates to a synthesis method of N-alkyl-beta-aminopropionate, in particular to a synthesis, separation and purification method of N-alkyl-beta-aminopropionate, and belongs to the technical field of organic synthesis.

Background

Sodium N-alkyl-beta-aminopropionate plays an important role in the development of pharmaceutical preparations, pesticide auxiliaries, personal care products and the like. Especially in the cosmetic industry, the molecular structure of the N-long chain alkyl derivative has the dual characteristics of amino and carboxyl, so that the N-long chain alkyl derivative has the unique advantages of not only being used as a high-efficiency humectant to maintain the moisture balance of a horny layer, but also playing the role of emulsion stabilization to promote the uniformity of a formula, and simultaneously having the pH buffering capacity and the mild antibacterial property. Such products, represented by sodium lauroaminopropionate, have become an irreplaceable multifunctional additive in high-end skin care formulations by virtue of their excellent water solubility and chemical stability.

At present, the industrialized production of N-alkyl-beta-sodium aminopropionate mainly adopts a two-step synthesis path of alkylamine and different propylene monomers, and specifically comprises (1) a beta-propiolactone method, namely a beta-propiolactone method, wherein high-activity cyclic anhydride is used as a raw material, but the cost is high, (2) an acrylonitrile method, namely a nucleophilic substitution reaction relying on cyano needs strict temperature control, (3) a methyl acrylate method, namely an ester ammonolysis and saponification process, and (4) an acrylic acid direct condensation method, namely a precise pH value control. Although these processes have been commercialized, there are still common problems of low reaction selectivity, complex byproducts, heavy metal catalyst residues, etc., resulting in difficulty in meeting the standards of the final product purity, and restriction of industrial upgrading due to energy consumption and three-waste treatment cost.

In addition, the post-treatment process of the synthesis of the N-alkyl-beta-aminopropionic acid sodium in the prior art is relatively complex, for example, pure water with the mass of 10-15 times of alkyl primary amine is required to be added into the reaction liquid in China patent (CN 111848425A), then the organic solvent with the mass of 3-5 times of alkyl primary amine is used for multiple times of extraction, the incompletely reacted alkyl primary amine is removed, the cost of the method is high, and the removal of the organic solvent is a great challenge. In China patent (CN 108675936A), the crude product is firstly dried to remove redundant water, then is dissolved in ethanol, filtered to remove inorganic alkali while the solution is hot, and then is dried to obtain the purified product. Although the existing post-treatment modes are more, the common problems of organic solvent residues, more product impurities and the like exist, so that the purity of the product cannot meet the use requirement, and the product needs extremely high production cost.

Along with the strict regulations of global cosmetic supervision and the rapid increase of the demand of consumers for pure cosmetic, a novel green synthesis process with high atomic economy and remarkable process enhancement becomes an urgent industry demand, and has remarkable economic benefit and social value. However, the current method has a plurality of defects, including the problems of strict reaction requirements, high raw material cost, insufficient product purity and the like. Therefore, research and development of an efficient and environment-friendly synthesis process of the N-alkyl-beta-sodium aminopropionate are particularly critical and urgent.

Disclosure of Invention

Aiming at the defects existing in the prior art, the invention aims to provide a method for synthesizing, separating and purifying N-alkyl-beta-sodium aminopropionate, which has the advantages of simple operation, short flow, high product separation recovery rate and high purity, can reduce the production cost of the N-alkyl-beta-sodium aminopropionate, and meets the requirement of industrial production.

In order to achieve the technical aim, the invention provides a method for synthesizing, separating and purifying N-alkyl-beta-aminopropionate, which comprises the steps of sequentially carrying out addition reaction and saponification reaction on long-chain fatty amine and acrylate compounds to obtain saponification reaction liquid, regulating the temperature of the saponification reaction liquid to 55-70 ℃, simultaneously adding water and adopting acid liquor to regulate pH value to 3.0-5.0, fully stirring, standing for layering, separating an upper organic layer while the organic layer is still hot, regulating pH value to 0.5-1.5 by adopting acid liquor, cooling to realize layering, separating an upper product, and neutralizing by adopting alkali solution to obtain the N-alkyl-beta-aminopropionate.

The key of the technical scheme of the invention is that the improved separation and purification means are adopted to realize the efficient separation and purification of the N-alkyl-beta-aminopropionate, and the efficient separation and purification of the N-alkyl-beta-aminopropionate can be realized only by strictly regulating and controlling the pH, the temperature and other conditions of the saponification reaction liquid, so that the separation and purification process of the N-alkyl-beta-aminopropionate is greatly simplified, and the yield of the N-alkyl-beta-aminopropionate is improved. More specifically, the process of separating N-alkyl- β -aminopropionate from a saponification reaction liquid is a difficult problem in the prior art, and the separation of residual long-chain fatty amine in the saponification reaction liquid is mainly achieved by an extraction method at present, but the extraction process requires the introduction of a large amount of organic solvent, and at the same time, causes the prolongation of the post-treatment process flow, which is industrially disadvantageous. The saponification reaction liquid contains water, N-alkyl-beta-aminopropionate product, long-chain fatty amine and the like, emulsion is formed at room temperature, separation cannot be realized at all, the temperature of the saponification reaction liquid is regulated at about 60 ℃, meanwhile, the pH value of the saponification reaction liquid is regulated at about 4, obvious layering phenomenon of the emulsion can occur, the lower layer is a water phase, the upper layer is an oil phase, the oil phase is a compound formed by coating N-alkyl-beta-aminopropionate with cocoanut amine, thus primary oil phase separation can be realized, water-soluble impurities are removed, the oil phase is further regulated to about 1 by adopting acid liquor, the cocoanut amine coated on the surface of the N-alkyl-beta-aminopropionate forms quaternary ammonium salt under the action of the acid liquor, the solubility of the cocoanut amine coated on the surface of the N-alkyl-beta-aminopropionate is increased, so that the coated N-alkyl-beta-aminopropionate is gradually released, the N-alkyl-beta-aminopropionate is further acidified to be converted into N-alkyl-beta-aminopropionate with lower solubility, and the N-alkyl-beta-aminopropionate is further separated from the long-chain fatty amine, and the N-alkyl-beta-aminopropionate is further mixed with alkali liquor to obtain the alkaline solution. Therefore, the invention realizes the high-efficiency separation of the N-alkyl-beta-amino propionate product by only regulating the pH value, and has the advantages of higher recovery rate, simple operation flow and avoidance of the use of organic solvents.

As a preferred embodiment, the long chain fatty amine has the following molecular structural formula:

Wherein R ₁ is an aliphatic hydrocarbon group of C ₈~C₁₈. The aliphatic hydrocarbon of C ₈~C₁₈ may be a saturated aliphatic hydrocarbon, specifically, for example, an alkane of C ₈~C₁₈, and the carbon chain of the alkane may be straight or branched. The aliphatic hydrocarbon of C ₈~C₁₈ may also be an unsaturated aliphatic hydrocarbon, specifically, for example, an unsaturated aliphatic hydrocarbon containing an alkenyl group or an alkynyl group, the number of alkenyl groups or alkynyl groups contained in the carbon chain of the unsaturated aliphatic hydrocarbon is one or more, the number is not limited, and the position of the alkenyl group or alkynyl group in the carbon chain is also not limited. The long chain fatty amine is further preferably coco amine having high alkylation reactivity. Commercial cocoamines are themselves multicomponent mixed long chain fatty amines.

As a preferred embodiment, the structural formula of the acrylate compound is as follows:

;

Wherein R ₂ is C ₁~C₃ alkyl. The C ₁~C₃ alkyl group is specifically, for example, methyl, ethyl or propyl, and the shorter the carbon chain, the higher the saponification reactivity thereof, and thus methyl is more preferable.

As a preferable scheme, the addition reaction is carried out by heating and melting long-chain fatty amine into a liquid phase, and slowly dropwise adding an acrylic compound into the liquid phase for addition reaction. The addition reaction is carried out under the condition of no solvent, long-chain fatty amine is heated and melted into liquid phase, and then the long-chain fatty amine is used as a benign solvent, so that the complex post-treatment process caused by a large amount of solvent is avoided. Meanwhile, the acrylic ester compound is slowly added into the long-chain fatty amine for reaction, so that the long-chain fatty amine in the reaction system is relatively kept excessive, and side reactions are avoided.

As a preferable scheme, the adding rate of the acrylate compound is controlled to be 3-5 s per drop. The rate of acrylate addition is tightly controlled and if it is too fast, it can result in too high a local acrylate concentration and the formation of bis-addition products is easy.

As a preferable scheme, the molar ratio of the long-chain fatty amine to the acrylate compound is 1:1-5. The molar ratio of the long-chain fatty amine to the acrylate compound is more preferably 1:2-3. The yield of long-chain fatty amines can be increased by appropriately increasing the ratio of the acrylic compounds.

As a preferable scheme, the condition of the addition reaction is that the temperature is 20-110 ℃ and the time is 2-12 h. Too high or too low a temperature of the addition reaction is disadvantageous for both purposes, and too low a temperature results in a lower efficiency of the addition reaction, while too high a temperature increases the conversion rate of the dialkylation. Therefore, in a further preferred scheme, the condition of the addition reaction is that the temperature is 60-100 ℃ and the time is 4-10 h. Under the preferable reaction conditions, a higher yield of the addition reaction can be ensured.

As a preferable scheme, the saponification reaction condition is that a sodium hydroxide solution with the concentration of 20-50wt% is adopted as a saponification reagent, the temperature is 80-110 ℃, and the time is 2-3 hours.

As a preferable scheme, the addition amount of the water is 2-5 times of the mass of the long-chain fatty amine.

The molecular structure of the N-alkyl-beta-aminopropionate of the invention is shown below (taking N-alkyl-beta-aminopropionate sodium as an example):

Wherein R ₁ is C ₆~C₁₈ alkyl.

Compared with the prior art, the technical scheme of the invention has the beneficial technical effects that:

The synthesis, separation and purification method of the N-alkyl-beta-aminopropionate provided by the invention can realize the rapid and efficient separation of the N-alkyl-beta-aminopropionate product through simple operation, greatly simplify the separation and purification process flow, improve the yield of the N-alkyl-beta-aminopropionate, and compared with the existing extraction separation technology, the method can avoid introducing a large amount of organic solvents, simplify the operation flow and reduce the separation and purification cost.

Drawings

FIG. 1 is a nuclear magnetic resonance spectrum of sodium cocoamidopropionate of example 2.

FIG. 2 shows the results of the delamination of the saponification reaction liquid at different temperatures in comparative example 1.

FIG. 3 shows the results of the separation of the saponification reaction liquid at different pH values in comparative example 2.

FIG. 4 is a liquid phase diagram of sodium cocoamidopropionate of example 2.

Detailed Description

The following specific examples are intended to further illustrate the present invention, but not to limit the scope of the claims.

The terms used in the present invention generally have meanings commonly understood by those of ordinary skill in the art unless otherwise indicated.

The experimental methods used in the following examples are conventional methods unless otherwise specified.

Reagents, materials, instruments and the like used in the examples described below are commercially available unless otherwise specified.

The main chemical reaction equations involved in the invention are as follows:

Wherein R ¹ is a long chain alkyl of C ₆~C₁₈ and R ² is a short chain alkyl of C ₁~C₃.

The following optimization experiments take cocoamine and methyl acrylate as examples to explore the best reaction conditions.

The following optimization experiments are carried out according to the following procedures that 1mol of cocoamine is added into a reaction vessel, the temperature is raised to the temperature required by the reaction, methyl acrylate (3 equivalent) is slowly dripped into the reaction vessel, the dripping speed (4 drops/second) and the reaction temperature are controlled, the stable reaction is ensured, after the reaction is carried out for 8 hours, the spot plate detection is carried out, after the reaction is finished, an alkali solution (35% aqueous solution is prepared by using 1 molNaOH), the saponification is carried out (3 hours), water (2.5 times m _Cocoamine ) is added, the temperature is regulated to 60 ℃, hydrochloric acid is added to pH=4, stirring is stopped, the solution is subjected to static delamination, liquid separation is carried out while the solution is still hot, the upper layer is an organic layer, the lower layer is a water layer, the organic layer is continuously acidified to pH=1, the temperature is reduced to room temperature, the product is separated from the water layer, the upper layer product is raised to 60 ℃, and sodium hydroxide aqueous solution is added to regulate the pH=8, so as to obtain the sodium coco amino propionate.

The conditions of the experimental group were optimized and the yields of sodium cocoamidopropionate under the corresponding conditions were as follows:

Methyl acrylate, 2.0 equivalents.

B methyl acrylate, 3.0 equivalents.

Methyl acrylate, 3.5 equivalents.

It can be seen from experiments 1 to 10 that the efficiency of the addition reaction tends to increase and then decrease with increasing reaction temperature, but the effect is best in the range of 60 to 80 ℃, too high or too low temperature of the addition reaction is unfavorable for the addition reaction, too low temperature results in lower efficiency of the addition reaction, and too high temperature of the addition reaction results in improving hydrolysis of methyl acrylate in alkaline environment, so that the reaction temperature is preferably 80 ℃.

As can be seen from experimental groups 11 to 17, the yield of the addition reaction shows a tendency of increasing first and then gradually over the reaction time, and when the addition reaction time reaches 8 hours, the addition reaction time is continuously prolonged with little influence on the yield of the addition product, so that the reaction time is preferably 8 hours.

As can be seen from experiment group 18, the amount of methyl acrylate is increased by 2 and 3 equivalents, the product is obviously increased along with the increase of the amount, the yield is highest at 97% when the amount is 3 equivalents, the cocoamine is a mixture, and the reaction is thorough by properly increasing the amount of methyl acrylate due to different carbon chain proportions, so that the preferable reaction molar ratio is 1:3.

According to the optimized test result, the optimal experimental scheme is selected, namely, 1equiv cocoamine is adopted as a reaction raw material, 3equiv methyl acrylate is dripped at the temperature of 80 ℃, the reaction is continuously stirred for 8 hours until the raw material is completely reacted, saponification is continuously carried out at the temperature of 80 ℃, water (2.5 times m _Cocoamine ) is added after the saponification is completed, the temperature is reduced to 60 ℃, hydrochloric acid is added to the mixture until the pH value is=4, stirring is stopped, standing and layering are carried out on the solution, liquid separation is carried out while the solution is still hot, the upper layer is an organic layer, the lower layer is an aqueous layer, the organic layer is continuously acidified to the pH value of=1, the temperature is reduced to the room temperature, the product is separated from the aqueous layer, the temperature of the upper layer product is raised to 60 ℃, and sodium hydroxide aqueous solution is added to regulate the pH value to be 8, so as to obtain sodium coco aminopropionate.

The following examples were carried out under the optimal reaction conditions obtained in the above-described optimization experiments, mainly considering the effect of synthesizing sodium N-alkyl-beta-aminopropionate from different substrates under the optimal reaction conditions.

Example 1

1Mol of dodecylamine was added to the reaction vessel and the temperature was raised to 80 ℃. Slowly dropwise adding methyl acrylate (3 equivalent) into the reaction kettle after reaching the temperature, controlling the dropwise adding speed (4 s per drop) and the reaction temperature (80 ℃), ensuring stable reaction for 8 hours, detecting a dot plate, adding 1.0mol of NaOH to prepare a 33% aqueous solution for saponification after finishing the reaction, preserving the heat for 3 hours after finishing the dropwise adding, stopping heating, and cooling the reactant to the room temperature. The reaction was post-treated, water (2.5 times m _Cocoamine ) was added, the temperature was adjusted to 60 ℃, hydrochloric acid was added to ph=4, stirring was stopped, the solution was allowed to stand still for demixing, the upper layer was separated while hot, the organic layer was the organic layer, the lower layer was the aqueous layer, the organic layer was further acidified to ph=1, cooled to room temperature, the product was separated from the aqueous layer, the upper layer product was warmed to 60 ℃, and sodium hydroxide aqueous solution was added to adjust ph=8 to give sodium cocoamidopropionate in 97% yield with 98.5% purity.

Characterization of sodium coco aminopropionate:

¹H NMR (400 MHz, CDCl₃) δ 3.13 (t, J = 5.8 Hz, 2H), 2.96 – 2.84 (m, 2H), 2.67 (t, J = 5.8 Hz, 2H), 1.74 (ddd, J = 15.5, 11.2, 7.1 Hz, 2H), 1.30 – 1.17 (m, 17H), 0.83 – 0.78 (m, 3H).

¹³C NMR (101 MHz, CDCl₃) δ 174.90, 76.21, 47.44, 43.78, 31.80, 30.90, 28.62, 28.54, 28.49, 28.33, 28.10, 25.78, 24.83, 21.67, 13.11.

example 2

In the reaction vessel, 1mol of cocoamine (commercial starting material, a mixed amine product of 5 carbon chains of different length) was added and heated to 80 ℃. Slowly dripping methyl acrylate into the reaction kettle after reaching the temperature, controlling the dripping speed (4 seconds/drip) and the reaction temperature (80 ℃) and ensuring stable reaction. After the dripping is finished, the reaction is carried out for 8 hours, the spot plate is used for detection, after the reaction is finished, 1.0mol of NaOH is added to prepare a 33% aqueous solution for saponification, after the dripping is finished, the temperature is kept for 3 hours, the heating is stopped, and the reactant is cooled to the room temperature. The reaction product is subjected to post-treatment, water (2.5 times m _Cocoamine ) is added, the temperature is regulated to 60 ℃, hydrochloric acid is added to pH=4, stirring is stopped, the solution is subjected to static layering, liquid separation is carried out while the solution is still hot, the upper layer is an organic layer, the lower layer is an aqueous layer, the organic layer is continuously acidified to pH=1, the temperature is reduced to room temperature, a product is separated from the aqueous layer, the upper layer product is heated to 60 ℃, sodium cocoamidopropionate is obtained by adding sodium hydroxide aqueous solution to regulate the pH=8, the yield is 97%, and the impurity peak of the sodium cocoamidopropionate product can be seen to be lower through liquid chromatography.

Characterization of sodium cocoamidopropionate ：¹H NMR (400 MHz, Chloroform-d) δ 3.21 (q, J = 6.6 Hz, 1H), 2.84 (t, J = 5.8 Hz, 1H), 2.59 (t, J = 7.1 Hz, 1H), 2.45 – 2.15 (m, 1H), 1.47 (s, 1H), 1.24 (s, 17H), 0.86 (d, J = 7.0 Hz, 2H).

¹³C NMR (101 MHz, CDCl₃) δ 174.90, 76.21, 47.44, 43.78, 31.80, 30.90, 28.62, 28.54, 28.49, 28.33, 28.10, 25.78, 24.83, 21.67, 13.11.

Comparative example 1

The only difference compared to example 2 is that the reactants are worked up, water (2.5 times m _Cocoamine ) is added, the temperature is adjusted to different values, hydrochloric acid is added to ph=4, stirring is stopped, the solution is allowed to stand still for delamination, and the delamination results at different temperatures are shown in table 1 and fig. 2.

Comparative example 2

The only difference compared to example 2 is that the reactants are worked up, water (2.5 times m _Cocoamine ) is added, the temperature is adjusted to about 60 ℃, hydrochloric acid is added to adjust the pH to different values, stirring is stopped, the solution is allowed to stand still for delamination, and the delamination results at different pH are shown in Table 2 and FIG. 3.

Claims (9)

1. A method for synthesizing, separating and purifying N-alkyl-β-aminopropionate, characterized in that: a long-chain fatty amine and an acrylic acid compound are sequentially subjected to an addition reaction and a saponification reaction to obtain a saponification reaction solution; the saponification reaction solution is temperatureed to 55° C. to 70° C., water is added, and the pH value is adjusted to 3.0 to 5.0 with an acid solution; after thorough stirring, the solution is allowed to stand for separation, and the upper organic layer is separated while hot; the organic layer is further adjusted to a pH value of 0.5 to 1.5 with an acid solution, cooled to separate the layers, and the upper product is separated and neutralized with an alkaline solution to obtain N-alkyl-β-aminopropionate. 2. The method for synthesizing, separating and purifying an N-alkyl-β-aminopropionate according to claim 1, wherein: The molecular structural formula of the long-chain fatty amine is as follows: ; Wherein, _R1 is a _C8 ~ _C18 aliphatic hydrocarbon group; The structural formula of the acrylic acid compound is as follows: ; Wherein, R ₂ is a C ₁ ~C ₃ alkane group. 3. The method for synthesizing, separating and purifying N-alkyl-β-aminopropionate according to claim 1, wherein the addition reaction comprises heating and melting a long-chain fatty amine into a liquid phase, and slowly adding an acrylic acid compound dropwise into the liquid phase to carry out the addition reaction. 4. The method for synthesizing, separating and purifying N-alkyl-β-aminopropionate according to claim 3, wherein the addition rate of the acrylic acid ester compound is controlled to be 3-5 seconds per drop. 5. The method for synthesizing, separating and purifying N-alkyl-β-aminopropionate according to claim 3, wherein the molar ratio of the long-chain fatty amine to the acrylic acid compound is 1:1-5. 6. The method for synthesizing, separating and purifying an N-alkyl-β-aminopropionate according to any one of claims 1 to 5, wherein the addition reaction is carried out at a temperature of 20 to 110°C and for a time of 2 to 12 hours. 7. The method for synthesizing, separating and purifying N-alkyl-β-aminopropionate according to claim 6, wherein the addition reaction is carried out at a temperature of 60-100°C and for a time of 4-10 hours. 8. The method for synthesizing, separating and purifying N-alkyl-β-aminopropionate according to claim 1, wherein the saponification reaction is carried out under the following conditions: a sodium hydroxide solution with a concentration of 20-50 wt% is used as the saponification reagent, the temperature is 80-110° C., and the reaction time is 2-3 hours. 9. The method for synthesizing, separating and purifying N-alkyl-β-aminopropionate according to claim 1, wherein the amount of water added is 2 to 5 times the mass of the long-chain fatty amine.