阅读说明：本技术 一种利用微通道光反应技术实现苯基重氮乙酸乙酯与甲基苯胺n-h插入反应的方法 (Method for realizing N-H insertion reaction of ethyl phenyldiazoacetate and methylaniline by using micro-channel photoreaction technology ) 是由 郭凯 刘杰 邱江凯 覃龙州 袁鑫 孙蕲 段秀 张欣鹏 吴蒙雨 于 2021-08-31 设计创作，主要内容包括：本发明公开了一种利用微通道光反应技术实现苯基重氮乙酸乙酯与甲基苯胺N-H插入反应的方法,将式I所示的甲基苯胺及其衍生物、式Ⅱ所示的苯基重氮乙酸乙酯及其衍生物和溶剂的混合溶液泵入设有光源的微通道反应装置中反应,即得如式Ⅲ所示的化合物。本发明是一个全新的实现苯基重氮乙酸乙酯与甲基苯胺N-H插入反应的方法,只需在反应体系中加入光源就可以实现苯基重氮乙酸乙酯与甲基苯胺N-H插入。(The invention discloses a method for realizing N-H insertion reaction of ethyl phenyldiazoacetate and methylaniline by utilizing a microchannel photoreaction technology, which comprises the steps of pumping mixed solution of methylaniline and derivatives thereof shown in a formula I, ethyl phenyldiazoacetate and derivatives thereof shown in a formula II and a solvent into a microchannel reaction device provided with a light source for reaction to obtain a compound shown in a formula III. The invention is a brand new method for realizing the N-H insertion reaction of the ethyl phenyldiazoacetate and the methylaniline, and the insertion of the ethyl phenyldiazoacetate and the methylaniline can be realized only by adding a light source into a reaction system.)

1. A method for realizing N-H insertion reaction of ethyl phenyldiazoacetate and methylaniline by utilizing a microchannel photoreaction technology is characterized in that methylaniline shown in a formula I and derivatives thereof, ethyl phenyldiazoacetate shown in a formula II and mixed solution of the derivatives thereof and a solvent are pumped into a microchannel reaction device provided with a light source for reaction, and a compound shown in a formula III is obtained;

wherein R is¹And R²Each independently selected from-H, alkyl, alkoxy, fluoroalkyl, bromoalkyl, chloroalkyl, or halogen.

2. The method according to claim 1, wherein the concentration of the methylaniline or the derivative thereof represented by formula I in the mixed solution is 0.05 to 1 mmol/mL.

3. The method as claimed in claim 1, wherein the concentration of ethyl phenyldiazoacetate represented by formula II and its derivatives in the mixed solution is 0.05-2 mmol/mL.

4. The method as claimed in claim 1, wherein the molar ratio of the methylaniline and its derivatives represented by formula I to the ethyl phenyldiazoacetate and its derivatives represented by formula II in the mixed solution is 1: (1-5).

5. The method according to claim 1, wherein the solvent is any one or more of methanol, ethanol, acetonitrile, acetone, water, phosphate buffer, tetrahydrofuran, 1, 4-dioxane, dichloromethane, 1, 2-dichloroethane, N-dimethylpropyleneurea, N-dimethylformamide, N-dimethylacetamide and dimethylsulfoxide.

6. The method of claim 1, wherein the microchannel reactor device provided with the light source comprises a feed pump, a microchannel reactor, a light source, and a receiver; wherein, the feed pump, the microchannel reactor and the receiver are sequentially connected in series through pipelines, and the microchannel reactor is placed under the irradiation of a light source.

7. The method of claim 1, wherein the light source has an intensity of 5-60W.

8. The method as claimed in claim 1, wherein the light source has a wavelength of 435 and 577 nm.

9. The process according to claim 1, wherein the reaction temperature is 10-30 ℃.

10. The process according to claim 1, wherein the residence time of the reaction is between 30s and 2.6 h.

Technical Field

The invention belongs to the field of chemical synthesis, and particularly relates to a method for realizing N-H insertion reaction of ethyl phenyldiazoacetate and methylaniline by utilizing a micro-channel photoreaction technology.

Background

Diazo ethyl phenylacetate can be used as pesticide and medicine intermediate, and has wide application in organic synthesis. The N-H insertion of such diazo compounds provides a means for preparing a variety of related derivatives, and researchers have therefore also held great interest in studying related reaction methods.

At present, a method for realizing the insertion reaction of ethyl phenyldiazoacetate and methylaniline N-H by utilizing a microchannel photoreaction technology is rarely reported. Davies in 2018 reported the use of blue light to promote photolysis of aryldiazoacetates (chem.sci.,2018,9, 5112-5118). Although the reaction can also effectively realize the insertion of ethyl phenyldiazoacetate and methylaniline N-H and has a better substrate range, the reaction system needs to be heated to a high temperature, which is not favorable for the economic principle of the reaction and may cause certain obstruction to the subsequent industrial production. Thierry Ollevier reported in 2017 that copper catalyzed the reaction of alpha-diazo esters and alpha-diazoketone type carbons with insertion of Si-H and S-H bonds (chem.j.org.chem.2017,82, 3000-3010). Although this reaction allows the synthesis of ethyl phenyldiazoacetate derivatives under mild conditions, the reaction requires the addition of a metal catalyst and takes a long time. The prior insertion reaction of ethyl phenyldiazoacetate and N-H methylaniline has the defects of expensive catalyst, low atom utilization rate, environmental friendliness and the like, and the defects limit the application of the ethyl phenyldiazoacetate in industrialization. Therefore, it is very interesting to develop an insertion reaction of ethyl phenyldiazoacetate and methylaniline N-H with low energy consumption, mild reaction conditions, environmental friendliness and easy scale-up.

Disclosure of Invention

The purpose of the invention is as follows: the invention aims to solve the technical problem of the prior art and provides a method for realizing N-H insertion reaction of ethyl phenyldiazoacetate and methylaniline by utilizing a micro-channel photoreaction technology.

In order to solve the technical problem, the invention discloses a method for realizing N-H insertion reaction of ethyl phenyldiazoacetate and methylaniline by utilizing a microchannel photoreaction technology, which comprises the steps of pumping mixed solution of methylaniline shown in a formula I and derivatives thereof, ethyl phenyldiazoacetate shown in a formula II and derivatives thereof and a solvent into a microchannel reaction device provided with a light source for reaction to obtain a compound shown in a formula III;

wherein R is¹And R²Each independently selected from-H, alkyl, alkoxy, fluoroalkyl, bromoalkyl, chloroalkyl, or halogen; preferably, R¹And R²Each independently selected from-H, alkyl, alkoxy, fluoroalkyl, or halogen; further preferably, R¹And R²Each independently selected from-H, -CH₃、-CH₃O、-CF₃-Cl, -F or-Br.

Wherein, in the mixed solution, the concentration of the methylaniline shown in the formula I and the derivative thereof is 0.05-1mmol/mL, preferably 0.05-0.5mmol/mL, and more preferably 0.1-0.5 mmol/mL.

Wherein, the concentration of the ethyl phenyl diazoacetate shown in the formula II and the derivative thereof in the mixed solution is 0.05-2mmol/mL, and preferably 0.15-1 mmol/mL.

Wherein, in the mixed solution, the molar ratio of the methylaniline and the derivatives thereof shown in the formula I to the ethyl phenyl diazoacetate and the derivatives thereof shown in the formula II is 1: (1-5).

The solvent is any one or combination of more of methanol, ethanol, acetonitrile, acetone, water, phosphate buffer, tetrahydrofuran, 1, 4-dioxane, dichloromethane, 1, 2-dichloroethane, N-dimethylpropyleneurea, N-dimethylformamide, N-dimethylacetamide and dimethyl sulfoxide, preferably any one or combination of more of methanol, ethanol and dichloromethane, and further preferably dichloromethane.

As shown in fig. 1 and fig. 2, the microchannel reactor with the light source includes a feed pump, a microchannel reactor, a light source, and a receiver; wherein, the feed pump, the microchannel reactor and the receiver are sequentially connected in series through pipelines, and the microchannel reactor is placed under the irradiation of a light source.

Wherein, the microchannel reactor is of a pore channel structure, and the pore channel material is perfluoroalkoxy alkane (PFA) or polytetrafluoroethylene.

Wherein the inner diameter of the microchannel reactor is 0.5-1mm, preferably 0.6 mm.

Wherein the length of the microchannel reactor is 5-20 m.

Wherein the volume of the microchannel reactor is 1-15.7mL, and preferably 2 mL.

Wherein the pumping rate is 0.1-2 mL/min.

Wherein the intensity of the light source is 5-60W.

Wherein the wavelength of the light source is 435-.

Wherein the reaction temperature is 10-30 ℃, and room temperature is preferred.

Wherein the residence time of the reaction is 30s-2.6h, preferably 1-60min, more preferably 1-30min, even more preferably 1-15min, even more preferably 1-10min, and most preferably 10 min.

Has the advantages that: compared with the prior art, the invention has the following advantages:

(1) the invention is a brand new method for realizing the N-H insertion reaction of the ethyl phenyldiazoacetate and the methylaniline, and the insertion of the ethyl phenyldiazoacetate and the methylaniline can be realized only by adding a light source into a reaction system.

(2) The method can realize the insertion reaction of ethyl phenyldiazoacetate and methylaniline N-H under the room temperature condition without using a catalyst.

(3) The invention overcomes the problem that the prior art needs to use a transition metal catalyst, and reduces the reaction cost and the energy consumption cost.

(4) The system related by the invention has no solid insoluble substances, has no blockage problem of micro-reaction pore channels, is simple to operate and high in safety, and overcomes the defects of the traditional method.

(5) Compared with the existing reaction system, the reaction system related by the invention has the advantages of shortened reaction time, improved reaction conversion rate and yield, and high reaction continuity, and is favorable for continuous and uninterrupted scale-up production.

(6) The conversion rate of the raw materials is 88-97%, and the yield of the product can reach 71-95%.

Drawings

The foregoing and/or other advantages of the invention will become further apparent from the following detailed description of the invention when taken in conjunction with the accompanying drawings.

FIG. 1 is a schematic diagram of the reaction scheme of the present invention.

FIG. 2 is a diagram of a microchannel reactor apparatus.

FIG. 3 is a hydrogen spectrum of the compound obtained in example 1.

FIG. 4 is a carbon spectrum of the compound obtained in example 1.

FIG. 5 is a hydrogen spectrum of the compound obtained in example 7.

FIG. 6 is a carbon spectrum of the compound obtained in example 7.

FIG. 7 is a hydrogen spectrum of the compound obtained in example 8.

FIG. 8 is a carbon spectrum of the compound obtained in example 8.

FIG. 9 is a hydrogen spectrum of the compound obtained in example 9.

FIG. 10 is a carbon spectrum of the compound obtained in example 9.

FIG. 11 is a hydrogen spectrum of the compound obtained in example 10.

FIG. 12 is a carbon spectrum of the compound obtained in example 10.

FIG. 13 is a hydrogen spectrum of the compound obtained in example 11.

FIG. 14 is a carbon spectrum diagram of the compound obtained in example 11.

Detailed Description

The experimental methods described in the following examples are all conventional methods unless otherwise specified; the reagents and materials are commercially available, unless otherwise specified.

The light source in the microchannel reactor described in the examples below was a 5W lamp with a wavelength of 470 nm.

Example 1

0.0241g (0.2mmol,1.0equiv.) of N-methylaniline and 0.0570g of ethyl 2-diazo-2-phenylacetate (0.3mmol,1.5equiv.) were weighed, dissolved in 2mL of methanol, and loaded in a syringe as a reaction solution. The reaction liquid is pumped into a microchannel reaction device, and directly enters a microchannel reactor for reaction (the inner diameter is 0.6mm, the length of the light receiving is 7m, and the volume is 2mL), the pumping flow rate is 0.2mL/min, and the reaction residence time is 10 min. After completion of the reaction, TLC was carried out, and the reaction mixture was extracted with ethyl acetate and saturated brine (3X 25mL), and the organic layers were combined, dried over anhydrous sodium sulfate, and the solvent was removed by distillation under the reduced pressure and then subjected to silica gel column chromatography (petroleum ether: ethyl acetate) to give 48.98mg of the final product in 91% yield. The characterization data are as follows (fig. 3, fig. 4):¹H NMR(400MHz,Chloroform-d)δ7.40–7.33(m,3H),7.30–7.25(m,4H),6.88(d,J＝8.2Hz,2H),6.81(t,J＝7.3Hz,1H),4.31–4.21(m,2H),1.27(t,J＝7.1Hz,3H).¹³C NMR(100MHz,Chloroform-d)δ171.9,149.9,136.0,129.3,128.7,128.5,128.1,118.0,113.4,65.7,61.1,34.6,14.3.

example 2

0.0241g (0.2mmol,1.0equiv.) of N-methylaniline and 0.0570g of ethyl 2-diazo-2-phenylacetate (0.3mmol,1.5equiv.) were weighed, dissolved in 2mL of N, N-dimethylformamide, and loaded in a syringe as a reaction solution. The reaction liquid is pumped into a microchannel reaction device, and directly enters a microchannel reactor for reaction (the inner diameter is 0.6mm, the length of the light receiving is 7m, and the volume is 2mL), the pumping flow rate is 0.2mL/min, and the reaction residence time is 10 min. After completion of the reaction, TLC was carried out, and the reaction mixture was extracted with ethyl acetate and saturated brine (3X 25mL), and the organic layers were combined, dried over anhydrous sodium sulfate, and subjected to silica gel column chromatography (petroleum ether: ethyl acetate) after removing the solvent by distillation under the reduced pressure to obtain 44.14mg of a final product in 82% yield.

Example 3

0.0241g (0.2mmol,1.0equiv.) of N-methylaniline and 0.0570g of ethyl 2-diazo-2-phenylacetate (0.3mmol,1.5equiv.) were weighed, dissolved in 2mL of acetonitrile, and loaded in a syringe as a reaction solution. The reaction liquid is pumped into a microchannel reaction device, and directly enters a microchannel reactor for reaction (the inner diameter is 0.6mm, the length of the light receiving is 7m, and the volume is 2mL), the pumping flow rate is 0.2mL/min, and the reaction residence time is 10 min. After completion of the reaction, TLC was carried out, and the reaction mixture was extracted with ethyl acetate and saturated brine (3X 25mL), and the organic layers were combined, dried over anhydrous sodium sulfate, and subjected to silica gel column chromatography (petroleum ether: ethyl acetate) after removing the solvent by distillation under the reduced pressure to obtain 42.52mg of a final product in 79% yield.

Example 4

0.0241g (0.2mmol,1.0equiv.) of N-methylaniline and 0.0570g of ethyl 2-diazo-2-phenylacetate (0.3mmol,1.5equiv.) were weighed, dissolved in 2mL of dichloromethane, and loaded in a syringe as a reaction solution. The reaction liquid is pumped into a microchannel reaction device, and directly enters a microchannel reactor for reaction (the inner diameter is 0.6mm, the length of the light receiving is 7m, and the volume is 2mL), the pumping flow rate is 0.2mL/min, and the reaction residence time is 10 min. After completion of the reaction, TLC was carried out, and the reaction mixture was extracted with ethyl acetate and saturated brine (3X 25mL), and the organic layers were combined, dried over anhydrous sodium sulfate, and subjected to silica gel column chromatography (petroleum ether: ethyl acetate) after removing the solvent by distillation under the reduced pressure to obtain 51.68mg of a final product in 96% yield.

Example 5

0.0241g (0.2mmol,1.0equiv.) of N-methylaniline and 0.0570g of ethyl 2-diazo-2-phenylacetate (0.3mmol,1.5equiv.) were weighed, dissolved in 2mL of 1, 4-dioxane, and loaded in a syringe as a reaction solution. The reaction liquid is pumped into a microchannel reaction device, and directly enters a microchannel reactor for reaction (the inner diameter is 0.6mm, the length of the light receiving is 7m, and the volume is 2mL), the pumping flow rate is 0.2mL/min, and the reaction residence time is 10 min. After completion of the reaction, TLC was carried out, and the reaction mixture was extracted with ethyl acetate and saturated brine (3X 25mL), and the organic layers were combined, dried over anhydrous sodium sulfate, and subjected to silica gel column chromatography (petroleum ether: ethyl acetate) after removing the solvent by distillation under the reduced pressure to obtain 45.75mg of a final product in 85% yield.

Example 6

N-methylaniline (1.205 g, 10mmol,1.0equiv.) and 2.850g of ethyl 2-diazo-2-phenylacetate (15mmol,1.5equiv.) were weighed, dissolved in 20mL of dichloromethane, and loaded in a syringe as a reaction solution. The reaction solution is pumped into a microchannel reactor at the same time, and is directly fed into the microchannel reactor for reaction (the inner diameter is 0.6mm, the length of the light receiving area is 7m, and the volume is 2mL), the pumping flow rate is 0.2mL/min, and the reaction residence time is 10 min. After completion of the reaction, TLC detection was carried out, and the reaction solution was extracted with ethyl acetate and saturated brine (3X 25mL), and the organic layers were combined, dried over anhydrous sodium sulfate, and the solvent was removed by distillation under the reduced pressure, followed by silica gel column chromatography (petroleum ether: ethyl acetate) to obtain 2.5030g of a final product in 93% yield.

Example 7

0.0282g (0.2mmol,1.0equiv.) of 4-chloro-N-methylaniline and 0.0570g of ethyl 2-diazo-2-phenylacetate (0.3mmol,1.5equiv.) were weighed, dissolved in 2mL of dichloromethane, and loaded in a syringe as a reaction solution. Pumping the reaction liquid into a microchannel reaction device, directly feeding into a microchannel reactor for reaction (the inner diameter is 0.6mm, the length of the light receiving is 7m, and the volume is 2mL), pumping the reaction liquid at a flow rate of 0.2mL/min, and carrying out reverse reactionThe residence time should be 10 min. After completion of the reaction, TLC was carried out, and the reaction mixture was extracted with ethyl acetate and saturated brine (3X 25mL), and the organic layers were combined, dried over anhydrous sodium sulfate, and the solvent was removed by distillation under the reduced pressure and then subjected to silica gel column chromatography (petroleum ether: ethyl acetate) to give 55.16mg of the final product in 91% yield. The characterization data are as follows (fig. 5, fig. 6):¹H NMR(400MHz,Chloroform-d)δ7.41–7.33(m,3H),7.28–7.24(m,2H),7.23–7.17(m,2H),6.79(d,J＝9.0Hz,2H),5.57(s,1H),4.26(m,J＝7.0,3.6Hz,2H),2.76(s,3H),1.26(t,J＝7.1Hz,3H).¹³C NMR(100MHz,Chloroform-d)δ171.6,148.6,135.6,129.1,128.8,128.5,128.2,122.9,114.7,66.0,61.2,34.8,14.3.

example 8

0.0242g (0.2mmol,1.0equiv.) of 4-methyl-N-methylaniline and 0.0570g of ethyl 2-diazo-2-phenylacetate (0.3mmol,1.5equiv.) were weighed, dissolved in 2mL of dichloromethane, and loaded in a syringe as a reaction solution. The reaction liquid is pumped into a microchannel reaction device, and directly enters a microchannel reactor for reaction (the inner diameter is 0.6mm, the length of the light receiving is 7m, and the volume is 2mL), the pumping flow rate is 0.2mL/min, and the reaction residence time is 10 min. After completion of the reaction, TLC was carried out, and the reaction mixture was extracted with ethyl acetate and saturated brine (3X 25mL), and the organic layers were combined, dried over anhydrous sodium sulfate, and the solvent was removed by distillation under the reduced pressure and then subjected to silica gel column chromatography (petroleum ether: ethyl acetate) to give 50.96mg of the final product in 90% yield. The characterization data are as follows (fig. 7, fig. 8):¹H NMR(400MHz,Chloroform-d)δ7.31–7.19(m,5H),7.00(d,J＝8.4Hz,2H),6.73(d,J＝8.6Hz,2H),5.50(s,1H),4.23–4.10(m,2H),2.69(s,3H),2.19(s,3H),1.18(t,J＝7.1Hz,3H).¹³C NMR(100MHz,Chloroform-d)δ170.9,146.9,135.1,128.7,127.6,127.4,126.9,126.4,112.9,65.2,59.9,33.8,19.3,13.2.

example 9

0.0272g (0.2mmol,1.0equiv.) of 4-methoxy-N-methylaniline and 0.0570g of ethyl 2-diazo-2-phenylacetate (0.3mmol,1.5equiv.) were weighed out, dissolved in 2mL of dichloromethane, and loaded in a syringe as a reaction solution. The reaction liquid is pumped into a microchannel reaction device, and directly enters a microchannel reactor for reaction (the inner diameter is 0.6mm, the length of the light receiving is 7m, and the volume is 2mL), the pumping flow rate is 0.2mL/min, and the reaction residence time is 10 min. After completion of the reaction, TLC was carried out, and the reaction mixture was extracted with ethyl acetate and saturated brine (3X 25mL), and the organic layers were combined, dried over anhydrous sodium sulfate, and the solvent was removed by distillation under the reduced pressure and then subjected to silica gel column chromatography (petroleum ether: ethyl acetate) to give 55.64mg of the final product in 93% yield. The characterization data are as follows (fig. 9, fig. 10):¹H NMR(400MHz,Chloroform-d)δ7.41–7.27(m,5H),6.86(m,J＝9.3Hz,4H),5.44(s,1H),4.28–4.15(m,2H),3.77(s,3H),2.74(s,3H),1.23(t,J＝7.1Hz,3H).¹³C NMR(100MHz,Chloroform-d)δ171.9,152.9,144.6,136.1,128.6,128.06,116.6,114.66,67.66,60.96,55.7,35.8,14.3.

example 10

0.0214g (0.2mmol,1.0equiv.) of N-methylaniline and 0.0804g of ethyl 2- (4-bromophenyl) -2-diazoacetate (0.3mmol,1.5equiv.) were weighed, dissolved in 2mL of dichloromethane, and loaded in a syringe as a reaction solution. The reaction liquid is pumped into a microchannel reaction device, and directly enters a microchannel reactor for reaction (the inner diameter is 0.6mm, the length of the light receiving is 7m, and the volume is 2mL), the pumping flow rate is 0.2mL/min, and the reaction residence time is 10 min. After completion of the reaction, TLC was carried out, and the reaction mixture was extracted with ethyl acetate and saturated brine (3X 25mL), and the organic layers were combined, dried over anhydrous sodium sulfate, and the solvent was removed by distillation under the reduced pressure and then subjected to silica gel column chromatography (petroleum ether: ethyl acetate) to give 64.55mg of the final product in 93% yield. The characterization data are as follows (fig. 11, fig. 12):¹H NMR(400MHz,Chloroform-d)δ7.42(d,J＝8.4Hz,2H),7.21–7.16(m,2H),7.10(d,J＝8.4Hz,2H),6.84–6.67(m,3H),5.48(s,1H),4.21–4.10(m,2H),2.72(s,3H),1.18(t,J＝7.1Hz,3H).¹³C NMR(100MHz,Chloroform-d)δ171.3,149.7,135.1,131.8,130.1,129.3,122.1,118.4,113.7,65.45,61.3,34.8,14.3.

example 11

N-methylaniline (0.0214 g, 0.2mmol,1.0equiv.) and 0.0696g of methyl 2- (4- (tert-butyl) phenyl) -2-diazoacetate (0.3mmol,1.5equiv.) were weighed, dissolved in 2mL of dichloromethane, and loaded in a syringe as a reaction solution. The reaction solution is pumped into a microchannel reactor at the same time, and is directly fed into the microchannel reactor for reaction (the inner diameter is 0.6mm, the length of the light receiving area is 7m, and the volume is 2mL), the pumping flow rate is 0.2mL/min, and the reaction residence time is 10 min. After completion of the reaction, TLC was carried out, and the reaction mixture was extracted with ethyl acetate and saturated brine (3X 25mL), and the organic layers were combined, dried over anhydrous sodium sulfate, and the solvent was removed by distillation under the reduced pressure and then subjected to silica gel column chromatography (petroleum ether: ethyl acetate) to give 54.77mg of the final product in 88% yield. The characterization data are as follows (fig. 13, fig. 14):¹H NMR(400MHz,Chloroform-d)δ7.30(d,J＝8.3Hz,2H),7.19(t,J＝8.0Hz,2H),7.12(d,J＝8.2Hz,2H),6.79(d,J＝8.3Hz,2H),6.72(t,J＝7.3Hz,1H),5.57(s,1H),3.69(s,3H),2.72(s,3H),1.24(s,9H).¹³C NMR(100MHz,Chloroform-d)δ172.6,151.1,149.9,129.3,132.7,,128.2,125.7,118.0,113.4,65.34,52.0,34.4,31.4.

comparative example 1

0.0241g (0.2mmol,1equiv) of N-methylaniline, 0.0570g of ethyl 2-diazo-2-phenylacetate (0.3mmol,1.5equiv.) were weighed out, and the mixture was charged into a Schlenk reaction tube, and after replacing argon three times, 2mL of methylene chloride was added. After 3 hours of reaction at room temperature, TLC detection was carried out, the reaction solution was extracted with ethyl acetate and saturated brine (3X 25mL), the organic layers were combined, dried over anhydrous sodium sulfate, the solvent was removed by distillation under the reduced pressure, and silica gel column chromatography (petroleum ether: ethyl acetate) was carried out to give 46.29mg of a final product in 86% yield.

The present invention provides a method and a method for implementing the insertion reaction of ethyl phenyldiazoacetate and methylaniline N-H by using microchannel photoreaction technology, and the method and the way for implementing the technical scheme are many, and the above description is only a preferred embodiment of the present invention, it should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should be regarded as the protection scope of the present invention. All the components not specified in the present embodiment can be realized by the prior art.