A purification method for N-phenylglycine and its derivatives

Abstract

This invention discloses a method for purifying N-phenylglycine and its derivatives, comprising the following steps: dissolving N-phenylglycine or its derivatives in an organic solvent, adding deionized water, slowly adding acid solution dropwise while stirring, controlling the system temperature at 5-90℃, continuously stirring, and maintaining the system pH at 0-1; separating the organic solvent, maintaining the system temperature at 5-90℃, slowly adding an alkaline solution dropwise to the remaining aqueous solution while stirring, adjusting and maintaining the system pH to 4-5, stirring for 0.5 hours, during which N-phenylglycine or its derivatives continuously precipitate; filtering and drying the precipitated N-phenylglycine or its derivatives to obtain purified N-phenylglycine or its derivatives. The purification method of this invention is simple to operate, avoiding problems such as products being darker in color or lower in purity, or high-purity products darkening in color during storage. The purified compound has the characteristics of high purity, resistance to discoloration, and good storage stability.

Description

Technical Field

[0001] This invention relates to the field of functional materials research, specifically to a method for purifying N-phenylglycine and its derivatives. Background Technology

[0002] N-Phenylglycine compounds are important intermediates in the manufacture of indigo dyes, and also serve as pharmaceutical intermediates and important additives in photosensitive formulations for dry film photoresists. Typically, these compounds are obtained by reacting aniline or its derivatives with the corresponding chloroalkylcarboxylic acids. Due to the use of excess aniline as a reactant, trace amounts of aniline are unavoidably present in the final N-phenylglycine compounds. Aniline further oxidizes to benzoquinone and a series of complex products, causing the color of the N-phenylglycine compounds to gradually change from off-white to dark brown during storage. Furthermore, the compounds prepared by the above synthetic method have low purity and require further purification.

[0003] The typical purification method for this type of compound involves first adjusting the pH of the crude product to alkaline in an aqueous phase, then extracting the aqueous phase with an organic solvent, removing the organic solvent, and then adjusting the aqueous phase after washing with the organic solvent to acidity, causing the product to precipitate and be purified. While this method can improve purity, the compound still tends to turn brown over time. Both of these factors limit the use of this type of compound in subsequent processes. Summary of the Invention

[0004] Technical Problem to be Solved: To overcome the shortcomings of existing technologies, specifically addressing the issues of darker color and lower purity in the synthesized products of N-phenylglycine and its derivatives, or the darkening of color in high-purity products during storage, this invention aims to provide a purification method for N-phenylglycine and its derivatives. In a two-phase mixture of an organic solution of N-phenylglycine or its derivatives and water, the pH of the aqueous phase is first adjusted to 0-1, the organic phase is separated, and then the pH of the aqueous phase is adjusted to 4-5, precipitating the final product. The purification method provided by this invention is simple to operate, and the purified compound exhibits high purity, resistance to discoloration, and good storage stability.

[0005] Technical solution: A method for purifying N-phenylglycine and its derivatives, characterized by comprising the following steps: S1: dissolving N-phenylglycine or its derivatives in an organic solvent, adding deionized water, slowly adding acid solution dropwise while stirring, controlling the system temperature at 5-90℃, stirring continuously, and maintaining the system pH at 0-1;

[0006] S2: Separate the organic solvent, keep the system temperature at 5-90℃, slowly add the alkaline solution to the remaining aqueous solution while stirring, adjust and maintain the pH of the system to 4-5, stir for 0.5h, and N-phenylglycine or its derivatives will continuously precipitate during the stirring process;

[0007] S3: The precipitated N-phenylglycine or its derivative is filtered and dried to obtain purified N-phenylglycine or its derivative. Further, the general structural formula I of the N-phenylglycine and its derivative is shown below:

[0008]

[0009] Wherein, R is an alkyl or alkoxy group with 1-8 carbon atoms, a cycloalkyl group with 3-10 carbon atoms, an aryl or heteroaryl group with 6-10 carbon atoms, and R is connected in the ortho, meta, or para position of the nitrogen atom, and n is an integer from 1 to 6.

[0010] Furthermore, R is an alkyl group having 1-8 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, tert-pentyl, hexyl, heptyl, octyl, isooctyl, 2-ethylhexyl, etc., preferably an alkyl group having 1-3 carbon atoms.

[0011] Furthermore, R is an alkoxy group with 1-8 carbon atoms, such as methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, heptoxy, zincoxy, etc., preferably an alkoxy group with 1-3 carbon atoms.

[0012] Furthermore, R is a cycloalkyl group with 3-10 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, etc., preferably a cycloalkyl group with 5-7 carbon atoms.

[0013] Furthermore, R is an aryl group with 6-10 carbon atoms, such as phenyl, tolyl, xylyl, ethylphenyl, naphthyl, etc., preferably an aryl group with 6-8 carbon atoms.

[0014] Furthermore, R is a heteroaryl group with 6-10 carbon atoms, such as pyrrole, pyridinyl, piperidinyl, pyranyl, pyrazolyl, triazine, pyrrolidinyl, quinolinyl, isoquinolinyl, imidazolyl, benzimidazolyl, furanyl, benzofuranyl, indolyl, morpholinyl, etc., preferably a heteroaryl group with 6-8 carbon atoms.

[0015] Furthermore, n is an integer from 1 to 3.

[0016] Furthermore, the organic solvent includes dichloromethane, chloroform, dichloroethane, ethyl acetate, toluene, chlorobenzene, n-hexane, and cyclohexane, preferably dichloromethane, ethyl acetate, and chlorobenzene.

[0017] Furthermore, the amount of the organic solvent used is 2-20 times the mass of N-phenylglycine or its derivatives.

[0018] Furthermore, the amount of the organic solvent used is 6-10 times the mass of N-phenylglycine or its derivatives.

[0019] Furthermore, the mass ratio of the organic solvent to water is (1:5) to (5:1).

[0020] Furthermore, the mass ratio of the organic solvent to water is (1:2) to (2:1).

[0021] Furthermore, the system temperature in S1 is 25-35℃.

[0022] Furthermore, the acid solution is an acid solution with a mass fraction of 10-20%, and the acid includes sulfuric acid, hydrochloric acid, nitric acid, and phosphoric acid.

[0023] Furthermore, the system temperature in S2 is 10-20℃.

[0024] Furthermore, the alkaline solution is an alkaline solution with a mass fraction of 10-20%, and the alkali includes an aqueous solution of sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, sodium hydroxide, and potassium hydroxide, and 25-28 wt.% ammonia.

[0025] Beneficial effects:

[0026] 1. The purification method of the present invention avoids the problems of products having a darker color or lower purity, or high-purity finished products darkening in color during storage. The purified compound has the characteristics of high purity, not easy to change color, and good storage resistance.

[0027] 2. The purification method of this invention is simple to operate, and the purified compound has high purity and is not easily discolored, which makes the research of N-phenylglycine and its derivatives of great significance in the field of functional materials. Attached image description:

[0028] Figure 1 The HPLC chromatogram of Example 1;

[0029] Figure 2 These are photos of the crude product before purification, during initial purification, and after the purified product has been stored for 14 days in Example 1.

[0030] Figure 3 The HPLC chromatogram for Example 2 is shown below.

[0031] Figure 4 These are photos of the crude product before purification, during initial purification, and after the purified product has been stored for 14 days in Example 2.

[0032] Figure 5 The HPLC chromatogram for Example 3 is shown below.

[0033] Figure 6 These are photos of the crude product before purification, during initial purification, and after the purified product has been stored for 14 days in Example 3.

[0034] Figure 7 The HPLC chromatogram for Example 4 is shown below.

[0035] Figure 8 These are photos of the crude product before purification, during initial purification, and after 14 days of storage of the purified product in Example 4.

[0036] Figure 9 The HPLC chromatogram is for Comparative Example 1.

[0037] Figure 10 Photos of Comparative Example 1 before crude product purification, after initial purification, and after the purified product has been stored for 14 days. Detailed Implementation

[0038] The present invention will be further described below with reference to the embodiments. The following embodiments are explanations of the present invention and the present invention is not limited to the following embodiments.

[0039] The crude N-phenylglycine or its derivatives used in the following examples were synthesized by conventional methods using aniline or its derivatives and the corresponding chloroalkylcarboxylic acids. The crude products contained 94%-97% N-phenylglycine or its derivatives and were all light brown in color.

[0040] Example 1

[0041] The crude N-phenylglycine contains 96.3% N-phenylglycine.

[0042] A method for purifying N-phenylglycine and its derivatives, characterized by comprising the following steps:

[0043] S1: Dissolve 25.0g of crude N-phenylglycine in 150g of dichloromethane, add 150g of deionized water, and slowly add 10% dilute hydrochloric acid solution dropwise while stirring. Control the system temperature at 30℃ and adjust the pH of the system to 1.

[0044] S2: Continue stirring for 0.5 hours. If the pH is higher than 1, continue adding dilute hydrochloric acid until the pH of the system is 1.

[0045] S3: Separate the dichloromethane organic phase, lower the temperature of the remaining aqueous system to 15°C, and slowly add 10% sodium hydroxide aqueous solution dropwise while stirring to adjust the pH of the system to 5;

[0046] S4: Continue stirring for 0.5h. If the pH is lower than 4, continue adding sodium hydroxide solution until the pH of the system is 5. During this process, N-phenylglycine will continuously precipitate.

[0047] S5: The precipitated N-phenylglycine is filtered to obtain a wet product, which is then further dried in a vacuum drying oven to constant weight to obtain purified N-phenylglycine.

[0048] 21.2 g of white solid was obtained, with a yield of 84.8%. HPLC analysis showed a purity of 99.6% based on peak results. The purified sample remained white after being left at room temperature for 14 days.

[0049] Peak Results

[0050] Retention time (minutes) Altitude (microvolts) Area (microvolts * seconds) %area 1 1.567 668 3118 0.04 2 2.307 1357505 7330906 99.57 3 4.404 3540 27368 0.37 4 4.848 190 1295 0.02

[0051] Example 2

[0052] The crude N-(4-methylphenyl)glycine contains 94.7% N-(4-methylphenyl)glycine.

[0053] A method for purifying N-phenylglycine and its derivatives, characterized by comprising the following steps:

[0054] S1: Dissolve 30.0g of crude N-(4-methylphenyl)glycine in 210g of dichloromethane, add 260g of deionized water, and slowly add 10% dilute hydrochloric acid solution dropwise while stirring. Control the system temperature at 30℃ and adjust the pH of the system to 1.

[0055] S2: Continue stirring for 0.5 hours. If the pH is higher than 1, continue adding dilute hydrochloric acid until the pH of the system is 1.

[0056] S3: Separate the dichloromethane organic phase, lower the temperature of the remaining aqueous system to 15°C, and slowly add 10% sodium hydroxide aqueous solution dropwise while stirring to adjust the pH of the system to 5;

[0057] S4: Continue stirring for 0.5 hours. If the pH is lower than 4, continue adding sodium hydroxide solution until the pH of the system is 5. During this process, N-(4-methylphenyl)glycine will continuously precipitate out.

[0058] S5: The precipitated N-(4-methylphenyl)glycine is filtered to obtain a moist product, and then further dried in a vacuum drying oven to constant weight to obtain purified N-(4-methylphenyl)glycine.

[0059] 25.8 g of white solid was obtained, with a yield of 86.0%. HPLC analysis showed a purity of 99.5% based on peak results. The purified sample remained white after being left at room temperature for 14 days.

[0060] Peak Results

[0061] Retention time (minutes) Altitude (microvolts) Area (microvolts * seconds) %area 1 2.034 4090 747 0.05 2 2.179 4902 961 0.06 3 2.458 7879562 1258442 99.52 4 3.816 2871 419 0.04 5 6.767 25876 2216 0.33

[0062] Example 3

[0063] The crude N-(4-methoxyphenyl)glycine contains 95.2% N-(4-methoxyphenyl)glycine.

[0064] A method for purifying N-phenylglycine and its derivatives, characterized by comprising the following steps:

[0065] S1: Dissolve 30.0g of crude N-(4-methoxyphenyl)glycine in 240g of ethyl acetate, add 200g of deionized water, and slowly add 10% dilute hydrochloric acid aqueous solution dropwise while stirring. Control the system temperature at 30℃ and adjust the pH of the system to 1.

[0066] S2: Continue stirring for 0.5 hours. If the pH is higher than 1, continue adding dilute hydrochloric acid until the pH of the system is 1.

[0067] S3: Separate the organic phase of ethyl acetate, lower the temperature of the remaining aqueous system to 10-15℃, and slowly add 10% sodium carbonate aqueous solution dropwise while stirring to adjust the pH of the system to 5;

[0068] S4: Continue stirring for 0.5h. If the pH is lower than 4, continue adding sodium carbonate aqueous solution until the pH of the system is 5. During this process, N-(4-methoxyphenyl)glycine will continuously precipitate out.

[0069] S5: The precipitated N-(4-methoxyphenyl)glycine was filtered to obtain a wet product, and then further dried in a vacuum drying oven to constant weight to obtain purified N-(4-methoxyphenyl)glycine.

[0070] 26.8 g of white solid was obtained, with a yield of 89.3%. HPLC analysis showed a purity of 99.5% based on peak results. The purified sample remained white after being left at room temperature for 14 days.

[0071] Retention time (minutes) Altitude (microvolts) Area (microvolts * seconds) %area 1 2.712 5990 1048 0.05 2 2.882 2940 596 0.03 3 3.420 6247 659 0.05 4 5.211 5909 587 0.05 5 6.352 11462249 848078 99.47 6 7.640 7214 534 0.06 7 13.882 5934 289 0.05 8 14.632 19928 721 0.17 9 16.219 6832 219 0.06

[0072] Example 4

[0073] The crude N-(1,1'-biphenyl-4-yl)glycine contains 96.5% N-(1,1'-biphenyl-4-yl)glycine.

[0074] S1: Dissolve 25.0g of crude N-(1,1'-biphenyl-4-yl)glycine in 225g of dichloroethane, add 300g of deionized water, and slowly add 10% dilute hydrochloric acid aqueous solution dropwise while stirring. Control the system temperature at 30-35℃ and adjust the pH of the system to 1.

[0075] S2: Continue stirring for 0.5 hours. If the pH is higher than 1, continue adding dilute hydrochloric acid until the pH of the system is 1.

[0076] S3: Separate the dichloroethane organic phase, lower the temperature of the remaining aqueous system to 20°C, and slowly add 10% sodium hydroxide aqueous solution dropwise while stirring to adjust the pH of the system to 5;

[0077] S4: Continue stirring for 0.5 h. If the pH is lower than 4, continue adding sodium hydroxide solution until the pH of the system is 5. During this process, N-(1,1'-biphenyl-4-yl)glycine will continuously precipitate out.

[0078] S5: The precipitated N-(1,1'-biphenyl-4-yl)glycine was filtered to obtain a wet product, and then further dried in a vacuum drying oven to constant weight to obtain purified N-(1,1'-biphenyl-4-yl)glycine.

[0079] 20.8 g of white solid was obtained, with a yield of 83.2%. HPLC analysis showed a purity of 99.7% based on peak results. The purified sample remained white after being left at room temperature for 14 days.

[0080] Peak Results

[0081] Retention time (minutes) Altitude (microvolts) Area (microvolts * seconds) %area 1 1.817 6574 506 0.08 2 2.020 3292 211 0.04 3 2.753 7960 999 0.10 4 3.354 5976 367 0.07 5 3.907 8187474 797398 99.71

[0082] Comparative Example 1

[0083] This embodiment uses the same crude N-phenylglycine as in Example 1, but employs a traditional purification method, as detailed below:

[0084] S1: Weigh 25.0g of crude N-phenylglycine, add 150g of deionized water, and slowly add 10% sodium hydroxide aqueous solution dropwise while stirring. Control the system temperature at 25-30℃ and adjust the pH of the system to 13.

[0085] S2: Continue stirring for 0.5 hours. If the pH is lower than 12, continue adding sodium hydroxide solution until the pH of the system reaches 13.

[0086] S3: After adding 150g of dichloromethane and stirring and washing for 0.5h, separate the dichloromethane organic phase, lower the temperature of the remaining aqueous system to 15℃, and slowly add 10% dilute hydrochloric acid aqueous solution while stirring to adjust the pH of the system to 3.

[0087] S4: Continue stirring for 0.5h. If the pH is higher than 3, continue adding dilute hydrochloric acid until the pH of the system is 3. During this process, N-phenylglycine will continuously precipitate.

[0088] S5: The precipitated N-phenylglycine is filtered to obtain a wet product, which is then further dried in a vacuum drying oven to constant weight to obtain purified N-phenylglycine.

[0089] 19.7 g of white solid was obtained, with a yield of 78.8%. HPLC analysis showed a purity of 99.2% based on peak results. After being left at room temperature for 14 days, the purified sample changed color from white to light brown.

[0090] Peak Results

[0091] Retention time (minutes) Altitude (microvolts) Area (microvolts * seconds) %area 1 1.562 692 5601 0.07 2 1.896 261 3029 0.04 3 2.288 1368636 7692393 99.22 4 4.310 5929 48321 0.62 5 4.768 409 3173 0.04

[0092] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any way. Any person skilled in the art can make many possible variations and modifications to the technical solutions of the present invention, or modify them into equivalent embodiments, without departing from the spirit and technical essence of the present invention. Therefore, any simple modifications, equivalent substitutions, equivalent changes, and modifications made to the above embodiments based on the technical essence of the present invention, without departing from the content of the technical solutions of the present invention, shall still fall within the scope of protection of the present invention.

Claims

1. A method for purifying N-phenylglycine and its derivatives, characterized in that, Includes the following steps: S1: Dissolve N-phenylglycine or its derivatives in an organic solvent, add deionized water, slowly add acid solution dropwise while stirring, control the system temperature at 5-90℃, stir continuously, and maintain the system pH at 0-1; S2: Separate the organic solvent, keep the system temperature at 5-90℃, slowly add the alkaline solution to the remaining aqueous solution while stirring, adjust and maintain the pH of the system to 4-5, stir for 0.5h, and N-phenylglycine or its derivatives will continuously precipitate during the stirring process; S3: The precipitated N-phenylglycine or its derivatives are filtered and dried to obtain purified N-phenylglycine or its derivatives. The general structural formula I of the N-phenylglycine derivative is shown below: ； Wherein, R is an alkyl or alkoxy group with 1-8 carbon atoms, a cycloalkyl group with 3-10 carbon atoms, an aryl or heteroaryl group with 6-10 carbon atoms, and R is connected in the ortho, meta, or para position of the nitrogen atom, and n is an integer from 1 to 6.

2. The purification method for N-phenylglycine and its derivatives according to claim 1, characterized in that: The organic solvent is selected from at least one of dichloromethane, chloroform, dichloroethane, ethyl acetate, toluene, chlorobenzene, n-hexane, and cyclohexane.

3. The purification method for N-phenylglycine and its derivatives according to claim 1, characterized in that: The amount of the organic solvent used is 2-20 times the mass of N-phenylglycine or its derivatives.

4. The purification method for N-phenylglycine and its derivatives according to claim 3, characterized in that: The amount of the organic solvent used is 6-10 times the mass of N-phenylglycine or its derivatives.

5. The purification method for N-phenylglycine and its derivatives according to claim 1, characterized in that: The mass ratio of the organic solvent to water is (1:5) to (5:1).

6. The purification method for N-phenylglycine and its derivatives according to claim 5, characterized in that: The mass ratio of the organic solvent to water is (1:2) to (2:1).

7. The purification method for N-phenylglycine and its derivatives according to claim 1, characterized in that: The acid solution is an acid solution with a mass fraction of 10-20%, and the acid is sulfuric acid, hydrochloric acid, nitric acid, or phosphoric acid.

8. The purification method for N-phenylglycine and its derivatives according to claim 1, characterized in that: The system temperature in S2 is 10-20℃.

9. The purification method for N-phenylglycine and its derivatives according to claim 1, characterized in that: The alkaline solution is an alkaline solution with a mass fraction of 10-20%, and the alkali is an aqueous solution of sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, sodium hydroxide, and potassium hydroxide, and 25-28 wt.% ammonia.

Images