Method for synthesizing N-alkyl-beta-amino sodium propionate from alkylamine and 3-halogenated propionate

Abstract

The invention discloses a method for synthesizing N-alkyl-beta-sodium aminopropionate from alkylamine and 3-halogenated propionate, and belongs to the technical field of organic synthesis. The method comprises the following steps: dissolving long-chain fatty amine and an alkali catalyst in a solvent to form a uniform solution, slowly dropwise adding 3-halogenated propionate into the solution to carry out a substitution reaction, and after the substitution reaction is completed, adding a sodium hydroxide solution to carry out a hydrolysis reaction to obtain the N-alkyl-beta-amino sodium propionate. And the product is easy to separate, and the yield is high.

Description

Technical Field

[0001] The invention relates to a method for synthesizing sodium N-alkyl-β-aminopropionate, in particular to a method for synthesizing sodium N-alkyl-β-aminopropionate from alkylamine and 3-halopropionic acid ester, belonging to the technical field of organic synthesis. Background Art

[0002] Sodium N-alkyl-β-alanine is an important organic compound, which is widely used in medicine, pesticides, cosmetics and other fields. In particular, sodium N-long-chain alkyl-β-alanine is used as a moisturizer, emulsifier, antibacterial agent and skin care ingredient in the cosmetic field. It has good water solubility, stability and multiple functions. Its mechanism of action is related to the amino and carboxyl groups in its chemical structure, and it can interact with other ingredients to form a stable complex. As consumers' demand for cosmetic safety and functionality increases, the demand for this type of product is also increasing. Therefore, many researchers are committed to developing efficient and high-yield synthesis methods for sodium N-alkyl-β-alanine. Among the numerous products, the synthesis method of sodium lauryl aminopropionate is taken as an example, which mainly includes β-propiolactone method (see the following synthesis route ①), acrylonitrile method (see the following synthesis route ②), methyl acrylate method (see the following synthesis route ③), acrylic acid method (see the following synthesis route ④), etc. These methods use dodecylamine as the starting material, and react with relatively cheap acrylonitrile, acrylic acid, acrylate, and more expensive β-propiolactone, respectively, to synthesize sodium lauryl aminopropionate in two steps.

[0003]

[0004] At present, there have been many research reports on the synthesis of sodium lauryl aminopropionate, but most methods have problems such as complex operation, low yield, and harsh reaction conditions. Summary of the invention

[0005] In view of the defects of the prior art, the object of the present invention is to provide a method for synthesizing sodium N-alkyl-β-aminopropionate from alkylamine and 3-halopropionic acid ester, which is simple to operate, mild conditions, and the product is easy to separate, and can achieve high-yield synthesis of sodium N-alkyl-β-aminopropionate.

[0006] In order to achieve the above technical purpose, the present invention provides a method for synthesizing sodium N-alkyl-β-aminopropionate from an alkylamine and a 3-halopropionic acid ester. The method comprises the following steps: dissolving a long-chain fatty amine and an alkaline catalyst in a solvent to form a uniform solution, slowly dropping the 3-halopropionic acid ester into the solution to carry out a substitution reaction, and then adding a sodium hydroxide solution to carry out a hydrolysis reaction after the substitution reaction is completed to obtain sodium N-alkyl-β-aminopropionate.

[0007] In the process of synthesizing sodium N-alkyl-β-aminopropionate, the key lies in realizing a highly selective substitution reaction between a long-chain fatty amine and a 3-halogenated propionate. Since α-H of the 3-halogenated propionate has certain activity, it is easy to undergo α-β elimination to form an acrylate byproduct under the action of an alkali catalyst. The key to the technical solution of the present invention lies in: on the one hand, the long-chain fatty amine and the alkali catalyst are pre-dissolved in a solvent, and the alkali catalyst is used to improve the reaction activity of the long-chain fatty amine; on the other hand, the 3-halogenated propionate is controlled to slowly enter the solution system, so that the probability of the 3-halogenated propionate undergoing an intramolecular elimination reaction can be effectively avoided, and the 3-halogenated propionate is highly selectively converted into an N-alkyl-β-aminopropionate intermediate.

[0008] As a preferred solution, the long-chain fatty amine has the following molecular structure: ; The 3-halopropionic acid ester has the following molecular structure: ; Among them, R1 is C6~C 18 R2 is a C1~C3 alkyl group; X is I, Br or Cl.

[0009] As a preferred embodiment, the 3-halopropionic acid ester is further preferably a 3-chloropropionic acid ester having high substitution reaction activity.

[0010] As a preferred solution, the alkaline catalyst includes at least one of sodium hydroxide, potassium hydroxide, pyridine and potassium carbonate. The preferred alkaline catalysts can catalyze the substitution reaction between the long-chain fatty amine and the 3-halogenated propionate to proceed smoothly, but when sodium hydroxide is selected as the alkaline catalyst, the effect of catalyzing the substitution reaction is significantly better than other alkaline catalysts such as potassium hydroxide, pyridine and potassium carbonate.

[0011] As a preferred solution, the amount of the base catalyst is 50-200% of the molar amount of the long-chain fatty amine. As the amount of the base catalyst increases, the yield of the substitution reaction product increases first and then tends to be flat. When the amount of the base catalyst is increased to 150% of the molar amount of the long-chain fatty amine, further increasing the amount of the base catalyst has almost no effect on the increase in the yield of the substitution reaction product. Therefore, the amount of the base catalyst is further preferably 150-200% of the molar amount of the long-chain fatty amine.

[0012] As a preferred solution, the solvent includes at least one of water, ethanol, ethyl acetate, tetrahydrofuran, acetonitrile, and DMF. The solvent has a relatively large influence on the substitution reaction between the long-chain fatty amine and the 3-halogenated propionate. A large number of experiments have shown that the substitution reaction effect of using protic solvents is better than that of aprotic solvents. For example, using water or ethanol as a solvent is better than other aprotic solvents such as EA, THF, acetonitrile, and when using ethanol as a solvent, the effect of the substitution reaction is the best.

[0013] As a preferred embodiment, the molar ratio of the 3-halopropionate to the long-chain fatty amine is 1 to 2: 1. An appropriate excess of 3-halopropionate is beneficial to improving the conversion rate of the long-chain fatty amine, thereby improving the yield of the substitution reaction product. The molar ratio of the 3-halopropionate to the long-chain fatty amine is further preferably 1.1 to 1.5: 1.

[0014] As a preferred solution, the addition rate of the 3-halopropionate is controlled to be 1 to 10 seconds per drop. The addition rate of the 3-halopropionate needs to be strictly controlled. If the addition rate is too slow, the reaction efficiency is low. If the addition rate is too fast, the local concentration of the 3-halopropionate is too high, and elimination side reactions are prone to occur, thereby further reducing the utilization rate of the 3-halopropionate.

[0015] As a preferred solution, the conditions of the substitution reaction are: temperature of 25-100° C., time of 4-6 hours. Too high or too low a temperature of the substitution reaction is not favorable for the substitution reaction, too low a temperature leads to low efficiency of the substitution reaction, and too high a temperature of the substitution reaction increases the probability of intramolecular elimination reaction of 3-halopropionic acid ester, therefore, a further preferred temperature is 40-80° C.

[0016] As a preferred solution, the saponification reaction conditions are: temperature of 80-110° C. and time of 4-6 hours.

[0017] As a preferred solution, after a long-chain fatty amine and sodium hydroxide are dissolved in ethanol at a molar ratio of 1:1.1-1.5 to form a uniform solution, 3-halogenated propionate in an amount of 1.5-2.0 times the molar amount of the long-chain fatty amine is slowly added dropwise to the solution at a rate of 1-10 seconds per drop, and the mixture is reacted at 40-80° C. for 4-6 hours, and then a sodium hydroxide solution is added to react at a temperature of 80-110° C. for 0.5-1.5 hours, and then acetone is added to precipitate the product.

[0018] The molecular structure of sodium N-alkyl-β-aminopropionate of the present invention is as follows:

[0019] Among them, R1 is C6~C 18 of alkyl.

[0020] Compared with the prior art, the technical solution of the present invention has the following beneficial technical effects: The method for synthesizing sodium N-alkyl-β-aminopropionate provided by the invention has the characteristics of simple operation, mild conditions, easy separation of products, high yield and the like. DETAILED DESCRIPTION

[0021] The following specific examples are intended to further illustrate the present invention rather than to limit the scope of protection of the claims.

[0022] The terms used in the present invention, unless otherwise specified, generally have the meanings commonly understood by those of ordinary skill in the art.

[0023] Unless otherwise specified, the experimental methods used in the following examples are conventional methods.

[0024] Unless otherwise specified, the reagents, materials, instruments, etc. used in the following examples can be obtained from commercial sources.

[0025] The main chemical reaction equations involved in the present invention are as follows:

[0026] Among them, R 1 C6~C 18 The long chain alkyl group, R 2 is a C1~C3 short-chain alkyl group, and X is a halogen substituent.

[0027] The following optimization experiment uses dodecylamine and ethyl 3-chloropropionate as an example to explore the optimal reaction conditions.

[0028] The following optimization experiments were carried out according to the following process: 1 mol of dodecylamine and an appropriate amount of catalyst were added to the reaction vessel, 100 ml of solvent was added to the reaction vessel, the temperature was raised to the required reaction temperature to promote uniform mixing of the reactants, and then 3-chloropropionic acid ethyl ester (1.1 equivalent) was slowly added to the reactor, the drop rate (1 drop / s) and the reaction temperature were controlled to ensure a smooth reaction, and the reaction was performed after 5 hours of reaction, and the plate was tested. After the reaction was completed, the temperature was raised to 95°C, and an alkaline solution (1.1 mol NaOH was used to prepare a 35% aqueous solution) was added for saponification for 1 hour. After the saponification was completed, the heating was stopped and the reactants were cooled to room temperature. The reactants were post-treated, and 500 g of acetone was used for pulping and purification for 2 hours, and then filtered and dried to remove impurities and by-products to obtain high-purity sodium lauryl aminopropionate.

[0029] The conditions of the optimized experimental group and the yield of sodium N-dodecyl-β-aminopropionate under the corresponding conditions are as follows:

[0030] a: 3-chloropropionic acid ethyl ester, 1.0 equivalent.

[0031] b: 3-chloropropionic acid ethyl ester, 1.5 equivalents.

[0032] c: 3-chloropropionic acid ethyl ester, 2.0 equivalents.

[0033] It can be seen from experimental groups 1 to 4 that most alkaline catalysts such as sodium hydroxide, potassium hydroxide, pyridine, potassium carbonate, etc. can catalyze the substitution reaction smoothly, but the effect is best when sodium hydroxide is used as a catalyst.

[0034] It can be seen from experimental groups 1 and 5~10 that the substitution reaction can proceed smoothly in solvents such as water, ethanol, ethyl acetate, tetrahydrofuran, acetonitrile, DMF, etc., but the solvent also has a relatively large influence on the substitution reaction. A large number of experiments have shown that the substitution reaction effect using protic solvents is better than that using aprotic solvents. For example, using water or ethanol as a solvent is better than other aprotic solvents such as EA, THF, acetonitrile, etc., and when using ethanol as a solvent, the substitution reaction effect is the best.

[0035] It can be seen from experimental groups 1 and 11~14 that: with the increase of reaction temperature, the efficiency of the substitution reaction shows a trend of first increasing and then decreasing, and the best effect is in the range of 40~80℃. Too high or too low temperature of the substitution reaction is not conducive to the substitution reaction. If the temperature is too low, the efficiency of the substitution reaction is low, and if the temperature of the substitution reaction is too high, the probability of intramolecular elimination reaction of 3-halopropionic acid ester will increase.

[0036] It can be seen from experimental groups 1 and 15~17 that: as the amount of base catalyst continues to increase, the yield of the substitution reaction product shows a trend of first increasing and then tending to be flat. When the amount of base catalyst is increased to 150% of the molar amount of long-chain fatty amine, continuing to increase the amount of base catalyst has almost no effect on the increase in the yield of the substitution reaction product.

[0037] It can be seen from experimental groups 1 and 18 that an appropriate excess of 3-halopropionate can make up for the loss of a small amount of 3-halopropionate side reactions, which is beneficial to improve the conversion rate of long-chain fatty amines and thus improve the yield of the substitution reaction product. When the amount of ethyl 3-chloropropionate is 1.0 equivalent, the yield of the substitution reaction product reaches 89%, indicating that the selectivity of the α-β elimination reaction of ethyl 3-chloropropionate is relatively small, and most of the ethyl 3-chloropropionate undergoes β substitution reaction.

[0038] According to the above optimization test results, the best experimental scheme was screened out: the reaction raw materials are 1 equiv of long-chain fatty amine and 1.1 equiv of ethyl halopropionate, catalyzed by 1.1 equiv of sodium hydroxide, with an appropriate amount of ethanol as solvent, the reaction is continuously stirred at 60°C until the raw materials react completely, and saponification is carried out at 95°C.

[0039] The following examples were carried out under the best reaction conditions obtained from the above optimization experiment, mainly considering the effect of synthesizing sodium N-alkyl-β-aminopropionate under the best reaction conditions with different substrates.

[0040] Example 1 In the reaction vessel, add 1 mol of dodecylamine and 1.1 mol of NaOH, and then add 100 ml of EtOH as a solvent to the reaction vessel to promote uniform mixing of the reactants. After complete dissolution, heat to 60 ° C. After reaching the temperature, slowly add 3-chloropropionate to the reactor, control the drop rate (1 drop / second) and the reaction temperature (60 ° C) to ensure a smooth reaction. After the addition is completed, react for 5 hours, spot plate detection, after the reaction is completed, heat to 95 ° C, add 1.1 mol of NaOH to make a 35% aqueous solution for saponification for 1 hour, after the saponification is completed, stop heating, and cool the reactants to room temperature. The reactants are post-treated, 3 kg of acetone is used for pulping and purification for 2 hours, and then filtered, washed, dried, etc. to remove impurities and by-products to obtain high-purity sodium laurylamine propionate, and the yield obtained is 99%. 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, 7.1Hz, 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.

[0041] Example 2

[0042] In the reaction vessel, add 1 mol of octadecylamine and 1.1 mol of NaOH, and then add 100 ml of EtOH as a solvent to the reaction vessel to promote uniform mixing of the reactants. After complete dissolution, heat to 60 ° C. After reaching the temperature, slowly add 3-chloropropionate to the reactor, control the drop rate (1 drop / second) and the reaction temperature (60 ° C) to ensure a smooth reaction. After the addition is completed, react for 5 hours, spot plate detection, after the reaction is completed, heat to 95 ° C, add 1.1 mol of NaOH to make a 35% aqueous solution for saponification for 1 hour, after the saponification is completed, stop heating, and cool the reactants to room temperature. The reactants are post-treated, 3 kg of acetone is used for pulping and purification for 2 hours, and then filtered, washed, dried, etc. to remove impurities and by-products to obtain high-purity sodium octadecylaminopropionate, and the yield obtained is 94%.

[0043] Comparative Example 1 In a reaction vessel, add 1 mol of dodecylamine, 1.1 mol of NaOH, and 1.1 mol of 3-chloropropionate, and then add 100 ml of EtOH as a solvent to the reaction vessel to promote uniform mixing of the reactants. After complete dissolution, heat to 60°C for reaction for 5 hours, spot plate detection, and after the reaction is completed, heat to 95°C, add 1.1 mol of NaOH to make a 35% aqueous solution for saponification for 1 hour. After the saponification is completed, stop heating and cool the reactants to room temperature. The reactants are post-treated, and 3 kg of acetone is used for pulping and purification for 2 hours, and then filtered, washed, dried, etc. to remove impurities and by-products to obtain high-purity sodium dodecylaminopropionate, and the yield obtained is 68%.

[0044] This comparative example shows that when 3-chloropropionate is added to the reaction system at one time, the side reaction is relatively serious, which greatly reduces the yield of sodium dodecanedione propionate.

Claims

1. A method for synthesizing sodium N-alkyl-β-aminopropionate from an alkylamine and a 3-halopropionic acid ester, characterized in that: After a long-chain fatty amine and an alkali catalyst are dissolved in a solvent to form a uniform solution, 3-halogenated propionate is first slowly added dropwise to the solution to carry out a substitution reaction. After the substitution reaction is completed, a sodium hydroxide solution is added to carry out a hydrolysis reaction to obtain the product.

2. The method for synthesizing sodium N-alkyl-β-aminopropionate from an alkylamine and a 3-halopropionic acid ester according to claim 1, characterized in that: The long-chain fatty amine has the following molecular structure: ； The 3-halopropionate has the following molecular structure: ； in, R1 is C6~C 18 The alkyl group; R2 is a C1~C3 alkyl group; X is I, Br or Cl.

3. The method for synthesizing sodium N-alkyl-β-aminopropionate from an alkylamine and a 3-halopropionic acid ester according to claim 1, characterized in that: The alkaline catalyst includes at least one of sodium hydroxide, potassium hydroxide, pyridine and potassium carbonate.

4. The method for synthesizing sodium N-alkyl-β-aminopropionate from an alkylamine and a 3-halopropionic acid ester according to claim 1 or 3, characterized in that: The amount of the base catalyst used is 50-200% of the molar amount of the long-chain fatty amine.

5. The method for synthesizing sodium N-alkyl-β-aminopropionate from an alkylamine and a 3-halopropionic acid ester according to claim 1, characterized in that: The solvent includes at least one of water, ethanol, ethyl acetate, tetrahydrofuran, acetonitrile and DMF.

6. The method for synthesizing sodium N-alkyl-β-aminopropionate from an alkylamine and a 3-halopropionic acid ester according to claim 1, characterized in that: The molar ratio of the 3-halopropionate to the long-chain fatty amine is 1-2:

1.

7. The method for synthesizing sodium N-alkyl-β-aminopropionate from an alkylamine and a 3-halopropionic acid ester according to claim 1, characterized in that: The addition rate of the 3-halopropionic acid ester is controlled to be 1-10s per drop.

8. A method for synthesizing sodium N-alkyl-β-aminopropionate from an alkylamine and a 3-halopropionic acid ester according to claim 1, 2, 3, 5, 6 or 7, characterized in that: The conditions of the substitution reaction are: temperature of 25-100° C. and time of 4-6 hours.

9. The method for synthesizing sodium N-alkyl-β-aminopropionate from an alkylamine and a 3-halopropionic acid ester according to claim 1, characterized in that: The saponification reaction conditions are: temperature of 80-110° C. and time of 0.5-1.5 hours.

10. A method for synthesizing sodium N-alkyl-β-aminopropionate from an alkylamine and a 3-halopropionic acid ester according to claim 1, 2, 3, 5, 6, 7 or 9, characterized in that: After dissolving a long-chain fatty amine and sodium hydroxide in ethanol at a molar ratio of 1:1.1-1.5 to form a uniform solution, 3-halogenated propionate in an amount of 1.5-2.0 times the molar amount of the long-chain fatty amine is slowly added dropwise to the solution at a rate of 1-10 seconds per drop, reacting at 40-80° C. for 4-6 hours, then adding sodium hydroxide solution and reacting at 80-110° C. for 0.5-1.5 hours, and then adding acetone to precipitate the product.

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