CN109265360B - Synthetic method of alpha-aryl substituted glycine ester derivative - Google Patents

Synthetic method of alpha-aryl substituted glycine ester derivative Download PDF

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CN109265360B
CN109265360B CN201811276352.4A CN201811276352A CN109265360B CN 109265360 B CN109265360 B CN 109265360B CN 201811276352 A CN201811276352 A CN 201811276352A CN 109265360 B CN109265360 B CN 109265360B
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glycine ester
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aryl substituted
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ester derivative
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CN109265360A (en
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孙彬
金灿
邓家诚
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Zhejiang University of Technology ZJUT
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    • C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C227/14—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof
    • C07C227/16—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions not involving the amino or carboxyl groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
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    • C07—ORGANIC CHEMISTRY
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Abstract

The invention discloses a synthetic method of an alpha-aryl substituted glycine ester derivative, which comprises the following steps: dissolving a glycine ester compound shown in a formula (I), arylamine shown in a formula (II) and a photocatalyst in an organic solvent, reacting for 6-24 h at the temperature of 20-80 ℃ under the irradiation of visible light, and after the reaction is finished, separating and purifying a reaction system to obtain a target product, namely synthesizing the alpha-aryl substituted glycine ester derivative shown in the formula (III), wherein the reaction formula is as follows:
Figure DEST_PATH_IMAGE001
in the formulae (I), (II) and (III), R1Is H, methyl, ethyl, isopropyl, methoxy, chlorine or phenyl; r2Is C1‑C4Alkyl groups of (a); r3、R4Each independently represents H or C1‑C6Alkyl groups of (a); r5Is methyl, chlorine, bromine or fluorine. The method for synthesizing the photocatalytic alpha-aryl substituted glycine ester derivative has the advantages of easily available raw materials, good reaction regioselectivity, simplicity and convenience in operation, economy, environmental friendliness and the like, and is a green chemical synthesis method with a good application prospect.

Description

Synthetic method of alpha-aryl substituted glycine ester derivative
Technical Field
The invention relates to a synthetic method of an alpha-aryl substituted glycine ester derivative.
Background
Glycine derivatives are widely used in the fields of medicine and biology, have very important physiological functions in human and animal bodies, can participate in the synthesis of proteins and active molecules related to metabolism, and have multiple effects of detoxifying by the liver, treating gastrointestinal dysfunction, preventing gastric ulcer and arthritis and the like. However, the content of glycine derivatives in nature and its limitation seriously affect their application in pharmacological research, and thus the synthesis of glycine derivatives by chemical methods is of great research significance.
The existing synthesis method of the alpha-aryl substituted glycine derivative mainly comprises the following steps: prepared by dehydrocoupling reactions between indoles and glycine compounds, such as the literature: (I) chloride-catalyzed aerobic oxidative aryl of glycerol esters and amide derivatives (adv. Synth. Catal., 2014, 356, 411); prepared by dehydrocoupling reactions between phenols or phenol ethers and glycine ester compounds, such as the literature: dehydrogenic cross-linking reaction between betweensN-aryl α -amino acid esters and phenols or phenol derivatives for synthesis of α -aryl α -amino acid esters (org. Lett., 2016, 18, 1526); prepared by dehydrocoupling reactions between imidazole heterocycles and glycine ester compounds, for example in the literature: CuCl/air-mediated oxidative coupling of imidazole withNAryl glycerol esters (RSC adv., 2017, 7, 30152). By passingN,N-dehydrocoupling reaction between dimethylaniline and glycine ester compound, for example in the literature: capper (I) catalyzed sp3 C-H arylation of N-Arylglycine ester derivatives under aerobic conditions (ChemistrySelect, 2017, 2, 2241)。
The synthesis method for preparing the alpha-aryl substituted glycine ester derivative is mostly realized by a catalytic system combining metal copper with an oxidant, and has the problems of large oxidant dosage, metal residue and the like, so that the application of the catalytic system has certain limitation.
Disclosure of Invention
Aiming at the technical problems in the prior art, the invention aims to provide a method for synthesizing a photocatalytic alpha-aryl substituted glycine ester derivative, which replaces the traditional metal catalysis method with photocatalysis to realize the reaction under a milder condition.
A synthetic method of an alpha-aryl substituted glycine ester derivative is characterized in that a glycine ester compound shown in a formula (I), arylamine shown in a formula (II) and a photocatalyst are dissolved in an organic solvent, the glycine ester compound, arylamine and photocatalyst are reacted for 6-24 hours at the temperature of 20-80 ℃ under the irradiation of visible light, after the reaction is finished, a reaction system is separated and purified to obtain a target product, and the alpha-aryl substituted glycine ester derivative shown in a formula (III) is synthesized, wherein the reaction formula is as follows:
Figure 451763DEST_PATH_IMAGE002
in the formulae (I), (II) and (III), R1Is H, methyl, ethyl, isopropyl, methoxy, chlorine or phenyl; r2Is C1-C4Alkyl groups of (a); r3、R4Each independently represents H or C1-C6Alkyl groups of (a); r5Is methyl, chlorine, bromine or fluorine.
The synthesis method of the alpha-aryl substituted glycine ester derivative is characterized in that the molar ratio of the glycine ester compound shown in the formula (I) to the arylamine shown in the formula (II) is 1: 1-8.
The synthesis method of the alpha-aryl substituted glycine ester derivative is characterized in that the molar ratio of the glycine ester compound shown in the formula (I) to the photocatalyst is 1: 0.01 to 0.2.
The synthesis method of the alpha-aryl substituted glycine ester derivative is characterized in that the photocatalyst is eosin Y, methylene blue or Acr+-Mes ClO4 -。
The synthesis method of the alpha-aryl substituted glycine ester derivative is characterized in that visible light is white light, green light or blue light.
The synthesis method of the alpha-aryl substituted glycine ester derivative is characterized in that the organic solvent is acetonitrile, acetone, 1,2 dichloroethane or tetrahydrofuran.
The synthesis method of the alpha-aryl substituted glycine ester derivative is characterized in that the steps of separating and purifying a reaction system are as follows: adding water and an extracting agent into a reaction system, extracting and layering to obtain a water layer and an organic layer, adding anhydrous sodium sulfate into the organic layer for drying, concentrating the dried organic layer under reduced pressure, separating and purifying the obtained concentrate through column chromatography silica gel, collecting eluent which is a mixed solution of petroleum ether and ethyl acetate, and evaporating the eluent to remove the solvent to obtain the target product.
The synthesis method of the alpha-aryl substituted glycine ester derivative is characterized in that an extracting agent is dichloromethane or ethyl acetate, and dichloromethane is preferred.
The synthesis method of the alpha-aryl substituted glycine ester derivative is characterized in that in an eluent, the volume ratio of petroleum ether to ethyl acetate is 10-50: 1, and preferably 15-40: 1.
Compared with the prior art, the invention has the beneficial effects that:
1) the reaction adopts a photocatalysis reaction system without metal participation, the photochemical reaction takes light as an excitation means, avoids the harsh conditions of high temperature, high pressure and the like in the traditional thermochemistry, and has the characteristics of atom economy, high catalytic efficiency and the like.
2) The method has the advantages of good reaction selectivity, simple and convenient operation and high product yield. The reaction uses air as the oxidant and does not require any other chemical oxidizing agent.
The invention provides a method for synthesizing a photocatalytic alpha-aryl substituted glycine ester derivative. The method has the advantages of easily available raw materials, good reaction area selectivity, simple and convenient operation, economy, environmental protection and the like, and is a green chemical synthesis method with better application prospect.
Detailed Description
The present invention is further illustrated by the following examples, which should not be construed as limiting the scope of the invention.
Example 1
Ethyl 2- (p-toluidine) acetate (0.5 mmol, 96.6 mg),Nadding methylaniline (1.0 mmol, 107 mg) and methylene blue (0.025 mmol, 8 mg) into a 25 mL double-neck flask, adding tetrahydrofuran (5 mL) as a solvent, stirring, reacting for 8h at 40 ℃ in an air atmosphere under the irradiation of blue light emitted by an LED lamp with the power of 3W, and after the reaction is finished, carrying out reverse reactionAdding water and dichloromethane into a reaction system, extracting and layering to obtain a water layer and an organic layer, adding anhydrous sodium sulfate into the organic layer for drying, carrying out reduced pressure distillation and concentration on the dried organic layer to obtain a yellow oily substance, separating and purifying the obtained yellow oily substance by column chromatography silica gel, taking a mixed solution of petroleum ether and ethyl acetate with a volume ratio of 20:1 as an eluent, collecting eluent and evaporating the solvent to obtain 127mg of a yellow oily product, wherein the yield is 85%, and the target product is obtained, and the structural formula of the product is as follows:
Figure 306587DEST_PATH_IMAGE004
；
a yellow oil;1H NMR (400 MHz, CDCl3) δ 7.35 (d, J = 8.4 Hz, 2H), 7.00 (d, J = 8.0 Hz, 2H), 6.63 (d, J = 8.4 Hz, 2H), 6.57 (d, J = 8.0 Hz, 2H), 5.00 (s, 1H), 4.33-4.14 (m, 2H), 2.87 (s, 3H), 2.27 (s, 3H), 1.28 (t, J = 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 172.6, 149.2, 144.1, 129.7, 128.2, 127.0, 126.1, 113.6, 112.6, 61.4, 60.7, 30.7, 20.4, 14.1. HRMS: C18H22N2NaO2[M+Na]+; calculated: 321.1573, found: 321.1581。
example 2
Tert-butyl 2- (p-toluidine) acetate (0.5 mmol, 110.6 mg),Nadding methylaniline (0.6 mmol, 64.2 mg) and methylene blue (0.025 mmol, 8 mg) into a 25 mL double-neck flask, adding acetonitrile (5 mL) as a solvent, stirring, reacting for 12h at 50 ℃ in an air atmosphere under the irradiation of blue light emitted by an LED lamp with the power of 3W, adding water and dichloromethane into a reaction system after the reaction is finished, extracting and layering the mixture to obtain a water layer and an organic layer, adding anhydrous sodium sulfate into the organic layer for drying, concentrating the dried organic layer by reduced pressure distillation to obtain a yellow oily substance, separating and purifying the obtained yellow oily substance by column chromatography silica gel, taking a mixed solution of petroleum ether and ethyl acetate with the volume ratio of 40:1 as an eluent, collecting the eluent and evaporating the solvent to obtain 122mg of a yellow solid product with the yield of 75%, thus obtaining the target product, wherein the target product is preparedThe structural formula is as follows:
Figure 86324DEST_PATH_IMAGE006
；
characterization data: a yellow solid; melting point: 100.6-102.8 ℃;1H NMR (600 MHz, CDCl3): δ 7.29 (d, J = 9.6 Hz, 2H), 6.95 (d, J = 8.4 Hz, 2H), 6.61 (d, J = 8.4 Hz, 2H), 6.51 (d, J = 8.4 Hz, 2H), 4.85 (s, 1H), 2.85 (s, 3H), 2.22 (s, 3H), 1.41(s, 9H). 13C NMR (150 MHz, CDCl3) δ 171.7, 148.8, 144.2, 129.6, 128.1, 126.7, 113.5, 112.6, 112.5, 81.8, 61.0, 30.8, 27.9, 20.4. HRMS: C20H26N2NaO2 [M+Na]+; calculated: 349.1886, found: 349.1890。
example 3
Ethyl 2- (p-isopropylaniline) acetate (0.5 mmol, 110.6 mg),Nmethylaniline (0.8 mmol, 85.6 mg), methylene blue (0.05 mmol, 16 mg) were added to a 25 mL two-necked flask, 1, 2-dichloroethane (5 mL) was added as a solvent, and the mixture was stirred, reacted at 50 ℃ for 16 hours in an air atmosphere under irradiation of blue light from an LED lamp with a power of 3W, and after the reaction was completed,
adding water and dichloromethane into a reaction system, extracting and layering to obtain a water layer and an organic layer, adding anhydrous sodium sulfate into the organic layer for drying, carrying out reduced pressure distillation and concentration on the dried organic layer to obtain a yellow oily substance, separating and purifying the obtained yellow oily substance by column chromatography silica gel, taking a mixed solution of petroleum ether and ethyl acetate with a volume ratio of 20:1 as an eluent, collecting eluent and evaporating the solvent to obtain 102.7mg of a yellow oily product, wherein the yield is 63%, and the target product is obtained, and the structural formula of the product is as follows:
Figure 419216DEST_PATH_IMAGE008
；
characterization data: a yellow oil;1H NMR (400 MHz, CDCl3): δ 7.35 (d, J = 8.4 Hz, 2H), 7.05 (d, J = 8.4 Hz, 2H), 6.63 (d, J = 8.4 Hz, 2H), 6.58 (d, J = 8.4 Hz, 2H), 4.97 (s, 1H), 4.32-4.13 (m, 2H), 2.92-2.76 (m, 4H), 1.29-1.22 (m, 9H). 13C NMR (100 MHz, CDCl3) δ 172.6, 149.1, 144.4, 138.3, 128.2, 127.0, 126.2, 113.3, 112.6, 61.4, 60.7, 33.1, 30.7, 24.2, 14.1. HRMS: C20H26N2NaO2 [M+Na]+; calculated: 349.1886, found: 349.1878。
example 4
Ethyl 2- (p-anisidine) acetate (0.5 mmol, 104.6 mg),Nadding methylaniline (0.6 mmol, 64.2 mg) and eosin Y (0.025 mmol, 17 mg) into a 25 mL double-neck flask, adding acetonitrile (5 mL) as a solvent, stirring, reacting for 6h at 30 ℃ in an air atmosphere under the irradiation of blue light emitted by an LED lamp with the power of 3W, after the reaction is finished, adding water and ethyl acetate into a reaction system, extracting and layering to obtain an aqueous layer and an organic layer, adding anhydrous sodium sulfate into the organic layer for drying, concentrating the dried organic layer by reduced pressure distillation to obtain a yellow oily substance, separating and purifying the obtained yellow oily substance by column chromatography silica gel, taking a mixed solution of petroleum ether and ethyl acetate with the volume ratio of 15:1 as an eluent, collecting the eluent and distilling off the solvent to obtain 130.4mg of a yellow oily product with the yield of 83%, and obtaining the target product, wherein the structural formula of the yellow oily substance is as follows:
Figure 233589DEST_PATH_IMAGE010
；
characterization data: a yellow oil;1H NMR (400 MHz, CDCl3) δ 7.33 (d, J = 8.4 Hz, 2H), 6.78 (d, J = 8.8 Hz, 2H), 6.63-6.59 (m, 4H), 4.94 (s, 1H), 4.28-4.15 (m, 2H), 3.76 (s, 3H), 2.86 (s, 3H), 1.26 (t, J = 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 172.7, 152.4, 149.2, 140.6, 128.2, 126.1, 114.8, 114.7, 112.5, 61.4, 61.2, 55.7, 30.7, 14.1. HRMS: C18H22N2NaO3[M+Na]+; calculated: 337.1523, found: 337.1523。
example 5
2- (pair)Chloroaniline) ethyl acetate (0.5 mmol, 106.5 mg),Nadding methylaniline (1.0 mmol, 107 mg) and eosin Y (0.1 mmol, 69 mg) into a 25 mL double-neck flask, adding acetone (5 mL) as a solvent, stirring, reacting at 50 ℃ for 24 hours in an air atmosphere under the irradiation of green light emitted by an LED lamp with the power of 3W, adding water and ethyl acetate into a reaction system after the reaction is finished, extracting and layering the mixture to obtain an aqueous layer and an organic layer, adding anhydrous sodium sulfate into the organic layer for drying, concentrating the dried organic layer by reduced pressure distillation to obtain a yellow oily substance, separating and purifying the obtained yellow oily substance by column chromatography silica gel, taking a mixed solution of petroleum ether and ethyl acetate with the volume ratio of 20:1 as an eluent, collecting the eluent, and evaporating the solvent to obtain 60.4mg of a yellow oily product with the yield of 38%, thus obtaining the target product, wherein the structural formula of the target product is as follows:
Figure 56051DEST_PATH_IMAGE012
；
characterization data: a yellow oil;1H NMR (400 MHz, CDCl3) δ 7.31 (d, J = 8.8 Hz, 2H), 7.11 (d, J = 8.8 Hz, 2H), 6.62 (d, J = 8.4 Hz, 2H), 6.53 (d, J = 8.8 Hz, 2H), 4.95 (s, 1H), 4.31-4.10 (m, 2H), 2.86 (s, 3H), 1.27 (t, J = 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ172.2, 149.3, 144.8, 129.0, 128.1, 125.3, 122.4, 114.5, 112.6, 61.6, 60.3, 30.6, 14.1. HRMS: C17H19ClN2NaO2[M+Na]+; calculated: 341.1027, found: 341.1024。
example 6
Tert-butyl 2- (p-toluidine) acetate (0.5 mmol, 110.6 mg),Nmethyl-m-methylaniline (1.0 mmol, 121.1 mg), Acr+-Mes ClO4 -(0.015 mmol, 6.2 mg) is added into a 25 mL double-neck flask, then tetrahydrofuran (5 mL) is added as a solvent, the mixture is stirred, under the irradiation of blue light emitted by an LED lamp with the power of 3W, the mixture reacts for 16 hours at the temperature of 50 ℃ in the air atmosphere, after the reaction is finished,
adding water and dichloromethane into a reaction system,extracting and layering to obtain a water layer and an organic layer, adding anhydrous sodium sulfate into the organic layer for drying, concentrating the dried organic layer by reduced pressure distillation to obtain a yellow oily substance, separating and purifying the obtained yellow oily substance by column chromatography silica gel, taking a mixed solution of petroleum ether and ethyl acetate with a volume ratio of 35:1 as an eluent, collecting the eluent, and evaporating to remove the solvent to obtain 136.1mg of a white solid product, wherein the yield is 80%, and the target product is obtained, and the structural formula of the target product is as follows:
Figure 257838DEST_PATH_IMAGE014
；
characterization data: a white solid; melting point: 82.0-85.2 ℃;1H NMR (600 MHz, CDCl3): δ 7.22 (d, J = 8.4 Hz, 2H), 6.97 (d, J = 8.4 Hz, 2H), 6.53-6.47 (m, 3H), 6.45 (dd, J 1 = 8.4 Hz, J 2 = 3.0 Hz, 1H), 5.09 (s, 1H), 2.84 (s, 3H), 2.48 (s, 3H), 2.24 (s, 3H), 1.43 (s, 9H). 13C NMR (150 MHz, CDCl3) δ 172.1, 148.8, 144.4, 137.5, 129.7, 127.2, 126.7, 125.2, 114.5, 113.2, 110.4, 81.7, 57.6, 30.7, 27.9, 20.4, 19.7. HRMS: C21H28N2NaO4[M+Na]+; calculated: 363.2043, found: 363.2060。
example 7
Tert-butyl 2- (p-toluidine) acetate (0.5 mmol, 110.6 mg),Nmethyl-m-bromoaniline (1.5 mmol, 277.5 mg), Acr+-Mes ClO4 -(0.01 mmol, 4.1 mg) is added into a 25 mL double-neck flask, acetonitrile (5 mL) is added as a solvent, stirring is carried out, under the irradiation of blue light emitted by an LED lamp with the power of 3W, the reaction is carried out for 24 hours at the temperature of 30 ℃ in the air atmosphere, after the reaction is finished, water and dichloromethane are added into a reaction system, extraction and layering are carried out, a water layer and an organic layer are separated, anhydrous sodium sulfate is added into the organic layer for drying, the dried organic layer is concentrated by reduced pressure distillation to obtain yellow oily matter, the obtained yellow oily matter is separated and purified by column chromatography silica gel, the mixed liquid of petroleum ether and ethyl acetate with the volume ratio of 30:1 is used as an eluent, eluent is collected and the solvent is evaporatedObtaining 84.9mg of white solid product with the yield of 42 percent, and obtaining the target product, wherein the structural formula is as follows:
Figure 456738DEST_PATH_IMAGE016
；
characterization data: a white solid; melting point: 106.3-108.3 ℃;1H NMR (400 MHz, CDCl3): δ 7.24 (d, J = 8.4 Hz, 1H), 6.97 (d, J = 8.0 Hz, 2H), 6.85 (d, J = 2.4 Hz, 1H), 6.56-6.48 (m, 3H), 5.36 (s, 1H), 2.84 (s, 3H), 2.24 (s, 3H), 1.44 (s, 9H). 13C NMR (100 MHz, CDCl3) δ 171.1, 149.7, 143.8, 129.6, 128.3, 126.8, 125.8, 125.3, 115.8, 113.5, 112.4, 82.1, 59.6, 30.5, 27.9, 20.4. HRMS: C20H25BrN2NaO2 [M+Na]+; calculated: 427.0992, found: 427.0988。
example 8
Tert-butyl 2- (p-toluidine) acetate (0.5 mmol, 110.6 mg),Nmethylm-chloroaniline (1.0 mmol, 141.0 mg), eosin Y (0.025 mmol, 17.3 mg) were placed in a 25 mL two-necked flask, followed by addition of acetone (5 mL) as a solvent and stirring, under the irradiation of white light emitted by an LED lamp with the power of 3W, the reaction is carried out for 20 hours at the temperature of 40 ℃ in the air atmosphere, after the reaction is finished, adding water and dichloromethane into a reaction system, extracting and layering to obtain a water layer and an organic layer, adding anhydrous sodium sulfate into the organic layer for drying, carrying out reduced pressure distillation and concentration on the dried organic layer to obtain a yellow oily substance, separating and purifying the obtained yellow oily substance by column chromatography silica gel, taking a mixed solution of petroleum ether and ethyl acetate with a volume ratio of 25:1 as an eluent, collecting eluent and evaporating the solvent to obtain 81mg of a white solid product, wherein the yield is 45%, and the target product is obtained, and the structural formula of the target product is as follows:
Figure DEST_PATH_IMAGE018
；
characterization data: a white solid; melting point: 93.9-96.0 ℃;1H NMR (600 MHz, CDCl3): δ 7.24 (d, J = 8.4 Hz, 1H), 6.97 (d, J = 7.8 Hz, 2H), 6.64 (d, J = 2.4 Hz, 1H), 6.54 (d, J = 8.4 Hz, 2H), 6.45 (dd, J 1 = 8.4 Hz, J 2 = 2.4 Hz, 1H), 5.39 (s, 1H), 2.81 (s, 3H), 2.24 (s, 3H), 1.44 (s, 9H). 13C NMR (150 MHz, CDCl3) δ 171.2, 149.7, 143.9, 134.9, 129.7, 128.3, 126.9, 124.0, 113.5, 112.4, 111.9, 82.1, 57.3, 30.5, 27.9, 20.4. HRMS: C20H25ClN2NaO2 [M+Na]+; calculated: 383.1497, found: 383.1511。
example 9
Tert-butyl 2- (p-toluidine) acetate (0.5 mmol, 110.6 mg),Nmethylm-fluoroaniline (1.0 mmol, 125.0 mg), eosin Y (0.025 mmol, 51.9 mg) was placed in a 25 mL two-necked flask, followed by addition of tetrahydrofuran (5 mL) as a solvent and stirring, under the irradiation of white light emitted by an LED lamp with the power of 3W, reacting for 24 hours at the temperature of 50 ℃ in the air atmosphere, after the reaction is finished, adding water and dichloromethane into a reaction system, extracting and layering to obtain a water layer and an organic layer, adding anhydrous sodium sulfate into the organic layer for drying, carrying out reduced pressure distillation and concentration on the dried organic layer to obtain a yellow oily substance, separating and purifying the obtained yellow oily substance by column chromatography silica gel, taking a mixed solution of petroleum ether and ethyl acetate with a volume ratio of 20:1 as an eluent, collecting eluent and evaporating the solvent to obtain 105mg of a white solid product with the yield of 61%, and obtaining a target product, wherein the structural formula of the target product is as follows:
Figure DEST_PATH_IMAGE020
；
characterization data: a white solid; melting point: m.p. 95.1-97.9 ℃;1H NMR (400 MHz, CDCl3): δ7.21-7.17 (m, 1H), 6.98 (d, J = 8.0 Hz, 2H), 6.57 (d, J = 8.0 Hz, 2H), 6.38-6.31 (m, 2H), 5.21 (s, 1H), 2.84 (s, 3H), 2.24 (s, 3H), 1.44 (s, 9H). 13C NMR (100 MHz, CDCl3) δ 171.2, 161.9 (d, J C-F = 243.1 Hz), 150.6 (d, J C-F = 10.8 Hz), 143.8, 129.6, 128.3 (d, J C-F = 5.8 Hz), 127.0, 113.5, 108.9, 98.8 (d, J C-F= 25.9 Hz), 81.9, 54.3, 30.5, 27.8, 20.4. HRMS: C20H25FN2NaO2 [M+Na]+; calculated: 367.1792, found: 367.1791。
example 10
Tert-butyl 2- (p-toluidine) acetate (0.5 mmol, 110.6 mg),Nmethyl o-chloroaniline (0.75 mmol, 105.8 mg), methylene blue (0.05 mmol, 16 mg) were charged in a 25 mL two-necked flask, and acetonitrile (5 mL) was added as a solvent, followed by stirring, under the irradiation of blue light emitted by an LED lamp with the power of 3W, reacting for 18h at the temperature of 45 ℃ in the air atmosphere, after the reaction is finished, adding water and ethyl acetate into a reaction system, extracting and layering to obtain a water layer and an organic layer, adding anhydrous sodium sulfate into the organic layer for drying, carrying out reduced pressure distillation and concentration on the dried organic layer to obtain a yellow oily substance, separating and purifying the obtained yellow oily substance by column chromatography silica gel, taking a mixed solution of petroleum ether and ethyl acetate with a volume ratio of 15:1 as an eluent, collecting the eluent, and evaporating to remove a solvent to obtain a white solid product of 88.2mg, wherein the yield is 49%, and the target product is obtained, and the structural formula of the target product is as follows:
Figure DEST_PATH_IMAGE022
；
characterization data: a white solid; melting point: 106.7-108.9 ℃;1H NMR (400 MHz, CDCl3): δ 7.42 (s, 1H), 7.31 (d, J = 8.0 Hz, 1H), 6.97 (d, J = 8.0 Hz, 2H), 6.65 (d, J = 8.4 Hz, 1H), 6.53 (d, J = 8.4 Hz, 2H), 4.84 (s, 1H), 2.93 (s, 3H), 2.25 (s, 3H), 1.44 (s, 9H). 13C NMR (100 MHz, CDCl3) δ 171.1, 144.6, 143.8, 129.6, 127.7, 127.0, 126.9, 126.6, 119.1, 113.6, 110.6, 82.2, 60.6, 30.4, 27.9, 20.4. HRMS: C20H25ClN2NaO2 [M+Na]+; calculated: 383.1497, found: 383.1480。
example 11
Tert-butyl 2- (p-toluidine) acetate (0.5 mmol, 110.6 mg),Nisopropyl aniline (1.0 mmol, 135.1)mg), adding methylene blue (0.05 mmol, 16 mg) into a 25 mL double-neck flask, adding acetone (5 mL) as a solvent, stirring, reacting for 12h at 40 ℃ in an air atmosphere under the irradiation of blue light emitted by an LED lamp with the power of 3W, after the reaction is finished, adding water and ethyl acetate into a reaction system, extracting and layering the mixture to obtain a water layer and an organic layer, adding anhydrous sodium sulfate into the organic layer for drying, concentrating the dried organic layer by reduced pressure distillation to obtain a yellow oily substance, separating and purifying the obtained yellow oily substance by column chromatography silica gel, taking a mixed solution of petroleum ether and ethyl acetate with the volume ratio of 20:1 as an eluent, collecting the eluent, and evaporating the solvent to obtain 95.6mg of a white solid product, wherein the yield is 54%, and the target product is obtained, and the structural formula of the product is as follows:
Figure DEST_PATH_IMAGE024
；
characterization data: a white solid; melting point: 114.2-115.2 ℃;1H NMR (400 MHz, CDCl3): δ 7.28 (d, J = 8.4 Hz, 2H), 6.97 (d, J = 8.0 Hz, 2H), 6.60 (d, J = 8.0 Hz, 2H), 6.53 (d, J = 8.4 Hz, 2H), 4.85 (s, 1H), 3.72-3.57 (m, 1H), 2.24 (s, 3H), 1.43 (s, 9H), 1.25 (d, J = 5.2 Hz, 6H). 13C NMR (100 MHz, d 6-DMSO) δ 172.2, 148.3, 145.5, 129.6, 128.6, 125.2, 124.5, 113.5, 112.6, 80.9, 60.8, 43.4, 28.0, 22.9, 20.5. HRMS: C22H30N2NaO2 [M+Na]+; calculated: 377.2199, found: 377.2202。
example 12
Tert-butyl 2- (p-toluidine) acetate (0.5 mmol, 110.6 mg),Nadding cyclohexylaniline (1.0 mmol, 135.1 mg) and eosin Y (0.025 mmol, 17 mg) into a 25 mL double-neck flask, adding acetone (5 mL) as a solvent, stirring, reacting at 45 ℃ in an air atmosphere under the irradiation of white light emitted by an LED lamp with power of 3W for 12h, adding water and ethyl acetate into the reaction system after the reaction is finished, extracting and layering to obtain an aqueous layer and an organic layer, adding anhydrous sodium sulfate into the organic layer for drying, and drying the dried organic layerCarrying out reduced pressure distillation and concentration to obtain a yellow oily substance, separating and purifying the obtained yellow oily substance by column chromatography silica gel, taking a mixed solution of petroleum ether and ethyl acetate with a volume ratio of 20:1 as an eluent, collecting the eluent, and evaporating the solvent to obtain 122.2mg of a white solid product, wherein the yield is 62%, and the target product is obtained, and the structural formula of the product is as follows:
Figure DEST_PATH_IMAGE026
；
characterization data: a white solid; melting point: 100.3-103.1 ℃;1H NMR (400 MHz, CDCl3): δ 7.30 (d, J = 8.4 Hz, 2H), 6.99 (d, J = 8.4 Hz, 2H), 6.61 (d, J = 8.4 Hz, 2H), 6.57 (d, J = 8.4 Hz, 2H), 4.88 (s, 1H), 3.35-3.25 (m, 1H), 2.27 (s, 3H), 2.15-2.08 (m, 2H), 1.88-1.69 (m, 3H), 1.47-1.19 (m, 14H). 13C NMR (100 MHz, CDCl3) δ171.8, 147.1, 144.3, 129.6, 128.1, 126.7, 126.1, 113.5, 113.2, 81.7, 61.1, 51.8, 33.5, 27.9, 25.9, 25.0, 20.4. HRMS: C25H35N2O2 [M+H]+; calculated: 395.2693, found: 395.2696.
example 13
Tert-butyl 2- (p-toluidine) acetate (0.5 mmol, 110.6 mg),N,Ndiethylaniline (0.6 mmol, 89.5 mg), methylene blue (0.025 mmol, 8 mg) were charged into a 25 mL two-necked flask, and acetone (5 mL) was added as a solvent, followed by stirring, under the irradiation of blue light emitted by an LED lamp with the power of 3W, reacting for 24 hours at the temperature of 50 ℃ in the air atmosphere, after the reaction is finished, adding water and ethyl acetate into a reaction system, extracting and layering to obtain a water layer and an organic layer, adding anhydrous sodium sulfate into the organic layer for drying, carrying out reduced pressure distillation and concentration on the dried organic layer to obtain a yellow oily substance, separating and purifying the obtained yellow oily substance by column chromatography silica gel, taking a mixed solution of petroleum ether and ethyl acetate with a volume ratio of 40:1 as an eluent, collecting the eluent, and evaporating to remove a solvent to obtain a 105mg white solid product, wherein the yield is 57%, and the target product is obtained, and the structural formula of the target product is as follows:
Figure DEST_PATH_IMAGE028
；
characterization data: a white solid; melting point: 101.5-103.2 ℃;1H NMR (400 MHz, CDCl3): δ 7.32 (d, J = 7.6 Hz, 2H), 6.98 (d, J = 8.0 Hz, 2H), 6.68 (d, J = 8.0 Hz, 2H), 6.55 (d, J = 8.0 Hz, 2H), 4.87 (s, 1H), 3.38 (q, J = 6.8 Hz, 4H), 2.25 (s, 3H), 1.45 (s, 9H), 1.20 (t, J = 6.8 Hz, 2H). 13C NMR (100 MHz, CDCl3) δ 171.9, 147.6, 144.4, 129.6, 128.1, 126.7, 124.4, 113.5, 111.8, 81.6, 61.0, 44.3, 27.9, 20.4, 12.6. HRMS: C23H33N2O2 [M+H]+; calculated: 369.2537, found: 369.2550。
the description is given for the sole purpose of illustrating embodiments of the inventive concept and should not be taken as limiting the scope of the invention to the particular forms set forth in the embodiments, but rather as being limited only to the equivalents thereof as may be contemplated by those skilled in the art based on the teachings herein.

Claims (10)

1. A synthetic method of an alpha-aryl substituted glycine ester derivative is characterized in that a glycine ester compound shown in a formula (I), arylamine shown in a formula (II) and a photocatalyst are dissolved in an organic solvent, the glycine ester compound, arylamine and photocatalyst are reacted for 6-24 hours at the temperature of 20-80 ℃ under the irradiation of visible light, after the reaction is finished, a reaction system is separated and purified to obtain a target product, and the alpha-aryl substituted glycine ester derivative shown in a formula (III) is synthesized, wherein the reaction formula is as follows:
Figure DEST_PATH_IMAGE002
in the formulae (I), (II) and (III), R1Is H, methyl, ethyl, isopropyl, methoxy, chlorine or phenyl; r2Is C1-C4Alkyl groups of (a); r3、R4Each independently represents H or C1-C6Alkyl groups of (a); r5Is methyl, chlorine, bromine or fluorine;
the photocatalyst is eosin Y, methylene blue or Acr+-Mes ClO4 -。
2. The method for synthesizing the alpha-aryl substituted glycine ester derivative according to claim 1, wherein the molar ratio of the glycine ester compound shown in the formula (I) to the arylamine shown in the formula (II) is 1: 1-8.
3. The method for synthesizing the alpha-aryl substituted glycine ester derivative according to claim 1, wherein the molar ratio of the glycine ester compound represented by the formula (I) to the photocatalyst is 1: 0.01 to 0.2.
4. The method as claimed in claim 1, wherein the visible light is white light, green light or blue light.
5. The method for synthesizing α -aryl substituted glycine ester derivatives as claimed in claim 1, wherein the organic solvent is acetonitrile, acetone, 1, 2-dichloroethane or tetrahydrofuran.
6. The method for synthesizing the alpha-aryl substituted glycine ester derivative as claimed in claim 1, wherein the steps of separating and purifying the reaction system are as follows: adding water and an extracting agent into a reaction system, extracting and layering to obtain a water layer and an organic layer, adding anhydrous sodium sulfate into the organic layer for drying, concentrating the dried organic layer under reduced pressure, separating and purifying the obtained concentrate through column chromatography silica gel, collecting eluent which is a mixed solution of petroleum ether and ethyl acetate, and evaporating the eluent to remove the solvent to obtain the target product.
7. The method for synthesizing the derivatives of α -aryl-substituted glycines ester as claimed in claim 6, wherein the extractant is dichloromethane or ethyl acetate.
8. The method for synthesizing the derivatives of α -aryl-substituted glycines according to claim 7, wherein the extracting agent is dichloromethane.
9. The method for synthesizing the alpha-aryl substituted glycine ester derivative as claimed in claim 6, wherein the volume ratio of the petroleum ether to the ethyl acetate in the eluent is 10-50: 1.
10. The method for synthesizing the alpha-aryl substituted glycine ester derivative as claimed in claim 9, wherein the volume ratio of petroleum ether to ethyl acetate in the eluent is 15-40: 1.
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