CN114315793B - Method for preparing S-diazoalkane compound by utilizing micro-channel reaction device - Google Patents

Abstract

The invention discloses a method for preparing S-diazoalkane compounds by utilizing a microchannel reaction device, which comprises the steps of reacting a first reaction liquid containing sulfoxide compounds shown in a formula II and diazo compounds shown in a formula III with a second reaction liquid containing trifluoromethanesulfonic anhydride in the microchannel reaction device to obtain a reaction liquid containing the S-diazoalkane compounds shown in the formula I. The reaction involved in the invention is a brand new method for synthesizing the S-diazoalkane compound, and has the advantages of high reaction yield, mild reaction condition, simple operation and good amplified synthesis potential.

Description

A method for preparing S-diazoalkane compounds using a microchannel reaction device

Technical Field

The invention belongs to the field of chemical synthesis, and in particular relates to a method for preparing S-diazoalkane compounds by using a microchannel reaction device.

Background Art

Traditional chemical reaction processes are mostly intermittent, with low reaction and separation efficiency, serious pollutant emissions, long process routes, and improper operation that can easily cause safety accidents, all of which seriously hinder the green and intelligent development of chemical production. Microfluidic reaction technology is a process intensification technology with reaction and dispersion feature scales at the hundred-micron level. This technology has built a "desktop factory" for traditional chemical industry, and also pointed out the direction for the green development of the chemical industry.

At present, there are few reports on the method of synthesizing S-diazoalkanes using microfluidic reaction technology. In 2018, Matthew J. Gaunt's group at the University of Cambridge reported a method for synthesizing high-valent iodinated diazoalkanes. This method uses (2,4-difluorophenyl)-λ ³ -iododiacetate and α-diazocarbonyl compounds as raw materials to synthesize the iodonium salt reagent of iodinated diazoalkanes (Nature, 2018, 562, 563–568). In 2021, Manuel Alcarazo's group reported for the first time a method for synthesizing S-diazoalkanes. This method uses sulfoxide compounds and ethyl diazoacetate as raw materials to synthesize S-diazoalkanes in the form of trifluoromethanesulfonates under ultra-low temperature conditions (Angew. Chem. Int. Ed. 2021, 60, 6943–6948). Although the above two methods successfully achieved the synthesis of the target compounds, they both have problems such as harsh reaction conditions, small synthesis scale, and low reaction yield. Therefore, it is of great significance to develop a method for the synthesis of S-diazoalkanes with mild reaction conditions, high product yield and easy scalability.

Summary of the invention

Purpose of the invention: The technical problem to be solved by the present invention is to provide a method for preparing S-diazoalkane compounds using a microchannel reaction device in view of the shortcomings of the prior art.

In order to solve the above technical problems, the present invention discloses a method for preparing S-diazoalkane compounds by using a microchannel reaction device, wherein a first reaction liquid containing a sulfoxide compound represented by formula II and a diazo compound represented by formula III and a second reaction liquid containing trifluoromethanesulfonic anhydride are reacted in a microchannel reaction device, and an effluent is collected to obtain a reaction liquid containing the S-diazoalkane compound represented by formula I, and the S-diazoalkane compound is obtained by post-treatment.

in,

R ¹ is selected from -H, methyl or halogen (-F, -Cl, -Br), preferably -H, methyl or -Cl, more preferably -H;

R ² is selected from an alkyl group, an alkyl derivative, a heterocyclic compound, an aryl group or an aryl derivative, preferably an alkyl group or a benzyl group (Bn), more preferably an alkyl group, and even more preferably -CH ₂ CH ₃ .

Wherein, the sulfoxide compound represented by formula II is preferably any one of the following compounds;

Wherein, the diazo compound represented by formula III is preferably ethyl diazoacetate and/or 2-benzyl diazoacetate.

Wherein, the S-diazoalkane compound represented by formula I is preferably any one of the following compounds;

The solvent of the first reaction liquid and the solvent of the second reaction liquid are independently selected from dichloromethane, acetone, 1,2-dichloroethane, acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide or a combination thereof, preferably dichloromethane.

Wherein, the molar concentration of the sulfoxide compound in the first reaction solution is 0.2-2.5 mmol/mL.

Wherein, the molar ratio of the sulfoxide compound to the diazo compound is 1:(1-5), preferably 1:1.2.

Wherein, the molar ratio of the sulfoxide compound to trifluoromethanesulfonic anhydride is 1:(1-5), preferably 1:1.2.

Wherein, the concentration of trifluoromethanesulfonic anhydride in the second reaction solution is 0.04-3 mmol/mL.

Among them, the microchannel reaction device includes a feed pump (Baoding Leifu Fluid Technology Co. Ltd, (TYD01-01-CE type)), a mixing module, a microchannel reactor and a receiver; wherein the feed pump is connected in series with the mixing module, the microchannel reactor and the receiver through a pipeline in sequence, see Figures 1 and 2.

Among them, the microchannel reactor is a channel structure, the number of channels increases or decreases as needed, the channel material is polytetrafluoroethylene or perfluoroalkoxyalkane (PFA), the size of the microchannel reactor is an inner diameter of 0.5 to 1.0 mm, preferably 0.6 mm; a length of 5 to 20 m; a volume of 1 to 15.7 mL, preferably 2.8 mL.

Wherein, the pumping rate ratio of the first reaction liquid to the second reaction liquid is 1:(0.5-1.5), preferably 1:1.

Wherein, the pumping rates of the first reaction liquid and the second reaction liquid are both 0.1-5.0 mL/min.

The reaction temperature is controlled to be -50 to 30°C, preferably -20 to 30°C, more preferably 20 to 30°C, and even more preferably room temperature.

The reaction time is 30 s to 2.6 h, preferably 5 min to 60 min, more preferably 5 min to 30 min, further preferably 5 min to 10 min, and most preferably 7 min.

Beneficial effects: Compared with the prior art, the present invention has the following advantages:

(1) The present invention synthesizes a new compound structure. The reagent can be prepared by reacting a sulfoxide compound, a diazo compound and trifluoromethanesulfonic anhydride in a microchannel reactor. The reaction has high yield, mild reaction conditions, simple operation, and good scale-up synthesis potential.

(2) The present invention can realize the synthesis of S-diazoalkane compounds at room temperature, avoiding the harsh ultra-low temperature conditions required by the original method and reducing the synthesis cost.

(3) The method used in the present invention can realize continuous synthesis, laying a foundation for scaled-up synthesis.

(4) The reactants of the present invention are accurately pumped in by a syringe pump, which avoids the dripping operation of the original method, simplifies the operation steps, and improves the safety of the process.

(5) The product synthesized by the present invention does not require column chromatography separation and can be obtained by recrystallization, thereby saving the solvent required for separation and reducing costs.

(6) The product conversion rate of the present invention is 78% to 96%, and the yield is as high as 66% to 83%.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG1 is a schematic diagram of the reaction flow of the present invention.

Figure 2 is a diagram of a microchannel reaction device.

FIG3 is a hydrogen spectrum of the product prepared in Example 1.

FIG4 is a carbon spectrum of the product prepared in Example 1.

FIG5 is a fluorine spectrum of the product prepared in Example 1.

FIG6 is a hydrogen spectrum of the product prepared in Example 5.

FIG. 7 is a carbon spectrum of the product prepared in Example 5.

FIG8 is a fluorine spectrum of the product prepared in Example 5.

FIG. 9 is a hydrogen spectrum of the product prepared in Example 6.

Figure 10 is a carbon spectrum of the product prepared in Example 6.

FIG11 is a fluorine spectrum of the product prepared in Example 6.

FIG12 is a hydrogen spectrum of the product prepared in Example 7.

Figure 13 is a carbon spectrum of the product prepared in Example 7.

FIG14 is a fluorine spectrum of the product prepared in Example 7.

FIG15 is a hydrogen spectrum of the product prepared in Example 8.

Figure 16 is a carbon spectrum of the product prepared in Example 8.

Figure 17 is the fluorine spectrum of the product prepared in Example 8.

FIG18 is a hydrogen spectrum of the product prepared in Example 9.

Figure 19 is a carbon spectrum of the product prepared in Example 9.

Figure 20 is the fluorine spectrum of the product prepared in Example 9.

Figure 21 is the hydrogen spectrum of the product prepared in Example 10.

Figure 22 is a carbon spectrum of the product prepared in Example 10.

Figure 23 is the fluorine spectrum of the product prepared in Example 10.

DETAILED DESCRIPTION

The present invention can be better understood according to the following examples. However, it is easy for those skilled in the art to understand that the contents described in the examples are only used to illustrate the present invention, and should not and will not limit the present invention described in detail in the claims.

Example 1

Weigh 2.02g (10.0mmol, 1.0equiv) of diphenyl sulfoxide and 1.26mL (12.0mmol, 1.2equiv) of ethyl diazoacetate, dissolve them in dichloromethane, and prepare a 10.0mL solution as the first reaction solution. Measure 2.02mL of trifluoromethanesulfonic anhydride (12.0mmol, 1.2equiv), dissolve them in dichloromethane, and prepare a 10.0mL solution as the second reaction solution. The first reaction solution and the second reaction solution are pumped into a microchannel reactor (with an inner diameter of 0.6mm and a volume of 2.8mL) at the same time. The pumping flow rate of the first reaction solution and the second reaction solution is 0.2mL/min. The reaction is carried out at -50°C for a residence time of 7.0min. After the reaction is completed, TLC detection is performed, the solvent is removed by distillation under reduced pressure and recovered, and the final product 2.96g is obtained by recrystallization from dichloromethane and ether, with a yield of 66% and a diphenyl sulfoxide conversion rate of 80%. As shown in Figures 3, 4 and 5, the characterization data are as follows: ¹ H NMR (400 MHz, Chloroform-d) δ7.95-7.84 (m, 4H), 7.76 (t, J = 7.4 Hz, 2H), 7.72-7.65 (m, 4H), 4.30 (q, J = 7.1 Hz, 2H), 1.27 (t, J = 7.1 Hz, 3H). ¹³ C NMR (100 MHz, Chloroform-d) δ159.1, 134.7, 131.3, 130.6, 124.0, 120.7 (q, J = 18.5 Hz, 1C), 64.2, 14.0. ¹⁹ F NMR (376 MHz, Chloroform-d) δ78.31. HRMS (ESI) m/z: calcd for C ₁₆ H ₁₅ N ₂ O ₂ S ⁺ [M-OTf] ⁺ :299.0849,found:299.0847.

Example 2

Weigh 2.02g (10.0mmol, 1.0equiv) of diphenyl sulfoxide and 1.26mL (12.0mmol, 1.2equiv) of ethyl diazoacetate, dissolve them in dichloromethane, and prepare a 10.0mL solution as the first reaction solution. Measure 2.02mL of trifluoromethanesulfonic anhydride (12.0mmol, 1.2equiv), dissolve them in dichloromethane, and prepare a 10.0mL solution as the second reaction solution. The first reaction solution and the second reaction solution are pumped into a microchannel reactor (with an inner diameter of 0.6mm and a volume of 2.8mL) at the same time. The pumping flow rate of the first reaction solution and the second reaction solution is 0.2mL/min. The reaction is carried out at -20°C with a residence time of 7.0min. After the reaction is completed, TLC detection is performed, the solvent is removed by distillation under reduced pressure and recovered, and the final product 3.04g is obtained by recrystallization from dichloromethane and ether, with a yield of 68% and a diphenyl sulfoxide conversion rate of 82%.

Example 3

Weigh 2.02g (10.0mmol, 1.0equiv) of diphenyl sulfoxide and 1.26mL (12.0mmol, 1.2equiv) of ethyl diazoacetate, dissolve them in dichloromethane, and prepare a 10.0mL solution as the first reaction solution. Measure 2.02mL of trifluoromethanesulfonic anhydride (12.0mmol, 1.2equiv), dissolve them in dichloromethane, and prepare a 10.0mL solution as the second reaction solution. The first reaction solution and the second reaction solution are pumped into a microchannel reactor (with an inner diameter of 0.6mm and a volume of 2.8mL) at the same time. The pumping flow rate of the first reaction solution and the second reaction solution is 0.2mL/min. The reaction is carried out at 0°C and the residence time is 7.0min. After the reaction is completed, TLC detection is performed, the solvent is removed by distillation under reduced pressure and recovered, and the final product 3.36g is obtained by recrystallization from dichloromethane and ether, with a yield of 75% and a diphenyl sulfoxide conversion rate of 88%.

Example 4

Weigh 2.02g (10.0mmol, 1.0equiv) of diphenyl sulfoxide and 1.26mL (12.0mmol, 1.2equiv) of ethyl diazoacetate, dissolve them in dichloromethane, and prepare a 10.0mL solution as the first reaction solution. Measure 2.02mL of trifluoromethanesulfonic anhydride (12.0mmol, 1.2equiv), dissolve them in dichloromethane, and prepare a 10.0mL solution as the second reaction solution. The first reaction solution and the second reaction solution are pumped into a microchannel reactor (with an inner diameter of 0.6mm and a volume of 2.8mL) at the same time. The pumping flow rate of the first reaction solution and the second reaction solution is 0.2mL/min. The reaction is carried out at room temperature for a residence time of 7.0min. After the reaction is completed, TLC detection is performed, the solvent is removed by distillation under reduced pressure and recovered, and the final product 3.71g is obtained by recrystallization from dichloromethane and ether, with a yield of 83% and a diphenyl sulfoxide conversion rate of 95%.

Example 5

Weigh 0.54g (2.0mmol, 1.0equiv) of 4,4'-dichlorodiphenyl sulfoxide and 0.25mL (2.4mmol, 1.2equiv) of ethyl diazoacetate, dissolve in dichloromethane, and prepare a 10.0mL solution as the first reaction solution. Measure 0.40mL of trifluoromethanesulfonic anhydride (2.4mmol, 1.2equiv), dissolve in dichloromethane, and prepare a 10.0mL solution as the second reaction solution. The first reaction solution and the second reaction solution are pumped into a microchannel reactor (with an inner diameter of 0.6mm and a volume of 2.8mL) at the same time. The pumping flow rate of the first reaction solution and the second reaction solution is 0.2mL/min. The reaction is carried out at room temperature with a residence time of 7.0min. After the reaction is completed, TLC detection is performed, the solvent is removed by distillation under reduced pressure and recovered, and the final product is obtained by recrystallization from dichloromethane and ether to obtain 0.78g of the final product with a yield of 76% and a conversion rate of 4,4'-dichlorodiphenyl sulfoxide of 88%. As shown in Figures 6, 7 and 8, the characterization data are as follows: ¹ H NMR (400 MHz, DMSO-d ₆ ) δ7.98 (d, J=8.8 Hz, 4H), 7.85 (d, J=8.8 Hz, 4H), 4.20 (q, J=7.0 Hz, 2H), 1.13 (t, J=7.0 Hz, 3H). ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ159.7, 139.6, 133.0, 131.0, 124.5, 63.9, 59.5, 14.3. ¹⁹ F NMR (376 MHz, Chloroform-d) δ77.78. HRMS (ESI) m/z: calcd for C ₁₆ H ₁₃ ClN ₂ O ₂ S ⁺ [M-OTf] ⁺ :367.0069,found:367.0067.

Example 6

Weigh 1.15g (5.0mmol, 1.0equiv) of 4,4'-dimethylbenzene sulfoxide and 0.63mL (6.0mmol, 1.2equiv) of ethyl diazoacetate, dissolve them in dichloromethane, and prepare a 10.0mL solution as the first reaction solution. Measure 1.0mL of trifluoromethanesulfonic anhydride (6.0mmol, 1.2equiv), dissolve them in dichloromethane, and prepare a 10.0mL solution as the second reaction solution. The first reaction solution and the second reaction solution are pumped into a microchannel reactor (with an inner diameter of 0.6mm and a volume of 2.8mL) at the same time. The pumping flow rate of the first reaction solution and the second reaction solution is 0.2mL/min. The reaction is carried out at room temperature with a residence time of 7.0min. After the reaction is completed, TLC detection is performed, the solvent is removed by distillation under reduced pressure and recovered, and the final product of 1.86g is obtained by recrystallization from dichloromethane and ether, with a yield of 78% and a conversion rate of 4,4'-dimethylbenzene sulfoxide of 89%. As shown in Figures 9, 10 and 11, the characterization data are as follows: 1H NMR (400 MHz, DMSO-d6) δ7.81 (d, J = 8.5 Hz, 4H), 7.57 (d, J = 8.4 Hz, 4H), 4.21 (q, J = 7.1 Hz, 2H), 2.44 (s, 6H), 1.14 (t, J = 7.1 Hz, 3H). 13C NMR (100 MHz, DMSO-d6) δ159.9, 145.4, 131.7, 130.9, 121.9, 63.8, 60.2, 21.4, 14.3. 19F NMR (376 MHz, Chloroform-d) δ77.78. HRMS (ESI) m/z: calcd for C ₁₈ H ₁₉ N ₂ O ₂ S ⁺ [M-OTf] ⁺ :327.1162,found:327.1152.

Example 7

Weigh 1.16g (5.0mmol, 1.0equiv) of thianthrene 5-oxide and 0.63mL (6.0mmol, 1.2equiv) of ethyl diazoacetate, dissolve in dichloromethane, and prepare 20.0mL solution as the first reaction solution. Measure 1.0mL of trifluoromethanesulfonic anhydride (6.0mmol, 1.2equiv), dissolve in dichloromethane, and prepare 20.0mL solution as the second reaction solution. The first reaction solution and the second reaction solution are pumped into a microchannel reactor (with an inner diameter of 0.6mm and a volume of 2.8mL) at the same time, and the pumping flow rate of the first reaction solution and the second reaction solution is 0.2mL/min. The reaction is carried out at room temperature for a residence time of 7.0min. After the reaction is completed, TLC detection is performed, the solvent is removed by distillation under reduced pressure and recovered, and the final product 1.96g is obtained by recrystallization from dichloromethane and ether, with a yield of 82% and a conversion rate of thianthrene 5-oxide of 95%. As shown in Figures 12, 13 and 14, the characterization data are as follows: ¹ H NMR (400 MHz, Chloroform-d) δ8.43 (d, J = 7.7 Hz, 2H), 7.91 (d, J = 7.7 Hz, 2H), 7.82 (t, J = 7.5 Hz, 2H), 7.72 (t, J = 7.6 Hz, 2H), 4.30 (q, J = 7.1 Hz, 2H), 1.28 (t, J = 7.1 Hz, 3H). ¹³ C NMR (100 MHz, Chloroform-d) δ159.6, 136.3, 135.2, 134.6, 130.4, 130.3, 120.8 (q, J = 318.7 Hz, 1C), 117.1, 64.3, 61.4, 14.1. ¹⁹ F NMR(376MHz,Chloroform-d)δ77.19.HRMS(ESI)m/z:calcdfor C ₁₆ H ₁₃ ClN ₂ O ₂ S ₂ ⁺ [M-OTf] ⁺ :329.0413, found:329.0406.

Example 8

Weigh 0.61g (2.0mmol, 1.0equiv) of 2,3,7,8-tetrafluorothianthrene 5-oxide and 0.25mL (2.4mmol, 1.2equiv) of ethyl diazoacetate, dissolve in dichloromethane, and prepare a 10.0mL solution as the first reaction solution. Measure 0.40mL of trifluoromethanesulfonic anhydride (2.4mmol, 1.2equiv), dissolve in dichloromethane, and prepare a 10.0mL solution as the second reaction solution. The first reaction solution and the second reaction solution are pumped into a microchannel reactor (with an inner diameter of 0.6mm and a volume of 2.8mL) at the same time. The pumping flow rate of the first reaction solution and the second reaction solution is 0.2mL/min. The reaction is carried out at room temperature with a residence time of 7.0min. After the reaction is completed, TLC detection is performed, the solvent is removed by distillation under reduced pressure and recovered, and the final product 0.91g is obtained by recrystallization from dichloromethane and ether, with a yield of 83% and a conversion rate of 2,3,7,8-tetrafluorothianthrene 5-oxide of 93%. As shown in Figures 15, 16 and 17, the characterization data are as follows: ¹ H NMR (400 MHz, DMSO-d ₆ )δ8.73–8.52 (m, 2H), 8.40–8.23 (m, 2H), 4.21 (q, J＝7.0 Hz, 2H), 1.16 (t, J＝7.0 Hz, 3H). ¹³ C NMR(100MHz,DMSO-d6)δ159.1,153.6(d,J＝13.3Hz,1C),151.1(t,J＝14.3Hz,2C),148.7(d,J＝13.8Hz,1C),129.6(d,J＝3.6Hz,1C),129.5(d,J＝3.4Hz,1C),121 .0(d,J＝23.0Hz,1C),119.4(d,J＝21.6Hz,1C),118.7(d,J＝2.6Hz,1C),118.6(d,J＝2.4Hz,1C),64.1,59.8,14.3. ¹⁹ F NMR (376MHz, Chloroform-d) δ77.83, 128.45 (d, J = 6.0Hz), 134.05 (d, J = 6.0Hz).

Example 9

Weigh 0.4 g (2.0 mmol, 1.0 equiv) of dibenzothiophene 5-oxide and 0.25 mL (2.4 mmol, 1.2 equiv) of ethyl diazoacetate, dissolve in dichloromethane, and prepare a 10.0 mL solution as the first reaction solution. Measure 0.4 mL of trifluoromethanesulfonic anhydride (2.4 mmol, 1.2 equiv), dissolve in dichloromethane, and prepare a 10.0 mL solution as the second reaction solution. The first reaction solution and the second reaction solution are pumped into a microchannel reactor (with an inner diameter of 0.6 mm and a volume of 2.8 mL) at the same time, and the pumping flow rate of the first reaction solution and the second reaction solution is 0.2 mL/min. The reaction is carried out at room temperature with a residence time of 7.0 min. After the reaction is completed, TLC detection is performed, the solvent is removed by vacuum distillation and recovered, and the final product 0.77 g is obtained by recrystallization from dichloromethane and ether, with a yield of 83% and a conversion rate of dibenzothiophene 5-oxide of 96%. As shown in Figures 18, 19 and 20, the characterization data are as follows: ¹ H NMR (400 MHz, DMSO-d ₆ ) δ8.52 (d, J=7.9 Hz, 2H), 8.39 (d, J=7.4 Hz, 2H), 7.94–7.85 (m, 2H), 7.79–7.71 (m, 2H), 3.78 (q, J=7.0 Hz, 2H), 0.74 (t, J=6.7 Hz, 3H). ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ158.9, 139.8, 134.2, 131.3, 131.2, 128.3, 124.1, 121.2 (q, J=20.4 Hz, 1C), 63.2, 60.6, 13.8. ¹⁹ F NMR(376MHz,Chloroform-d)δ77.74.HRMS(ESI)m/z:calcd forC ₁₆ H ₁₃ N ₂ O ₂ S ⁺ [M-OTf] ⁺ :297.0692, found:297.0688.

Example 10

Weigh 0.4 g (2.0 mmol, 1.0 equiv) of dibenzothiophene 5-oxide and 0.42 g (2.4 mmol, 1.2 equiv) of 2-diazoacetic acid benzyl ester, dissolve them in dichloromethane, and prepare 10.0 mL of solution as the first reaction solution. Measure 0.4 mL of trifluoromethanesulfonic anhydride (2.4 mmol, 1.2 equiv), dissolve them in dichloromethane, and prepare 10.0 mL of solution as the second reaction solution. The first reaction solution and the second reaction solution are pumped into a microchannel reactor (with an inner diameter of 0.6 mm and a volume of 2.8 mL) at the same time. The pumping flow rate of the first reaction solution and the second reaction solution is 0.2 mL/min. The reaction is carried out at room temperature with a residence time of 7.0 min. After the reaction is completed, TLC detection is performed, the solvent is removed by distillation under reduced pressure and recovered, and the final product 0.81 g is obtained by recrystallization from dichloromethane and ether, with a yield of 80% and a conversion rate of dibenzothiophene 5-oxide of 92%. As shown in Figures 21, 22 and 23, the characterization data are as follows: ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 8.50 (d, J = 7.8 Hz, 2H), 8.22 (d, J = 7.2 Hz, 2H), 7.84 (t, J = 7.3 Hz, 2H), 7.73 (t, J = 7.5 Hz, 2H), 7.38–7.15 (m, 3H), 6.87 (s, 2H), 4.80 (s, 2H). ¹³ CNMR (100 MHz, DMSO-d ₆ )δ158.9,139.6,134.5,134.2,131.2,131.0,129.0,128.8,128.7,128.3,124.1,121.2(q,J=320.4Hz,1C),68.4,60.7. ¹⁹ F NMR (376MHz, Chloroform-d)δ77.7 3.

Comparative Example 1

Weigh 2.02 g (10.0 mmol, 1.0 equiv) of diphenyl sulfoxide, dissolve it in 20.0 mL of dichloromethane, add 1.26 mL (12.0 mmol, 1.2 equiv) of ethyl diazoacetate, measure 2.02 mL of trifluoromethanesulfonic anhydride, and slowly drop it into the reaction solution. Stir the reaction at room temperature for 6 h, perform TLC detection after the reaction, remove the solvent by distillation under reduced pressure and recover it, and recrystallize it from dichloromethane and ether to obtain 2.96 g of the final product, with a yield of 66% and a diphenyl sulfoxide conversion rate of 80%.

Comparative Examples 2 to 6

Referring to Comparative Example 1, the reactions were carried out only according to the substrates in Examples 5 to 10 under the same conditions. The yields of the comparative examples are shown in Table 1.

Table 1

^[a] Reaction conditions: Weigh substrate 1 and substrate 2 separately, dissolve them in dichloromethane as reaction solution 1, and dissolve trifluoromethanesulfonic anhydride in dichloromethane as reaction solution 2. Pump them into a microchannel reactor at the same time for reaction. After the reaction, remove the solvent by distillation under reduced pressure, and recrystallize from dichloromethane and ether to obtain the product.

^[b] Reaction conditions: Weigh substrate 1 and substrate 2 separately, dissolve them in dichloromethane, slowly drop trifluoromethanesulfonic anhydride into the reaction solution, stir and react at room temperature for 6 hours, remove the solvent by vacuum distillation after the reaction, and recrystallize from dichloromethane and ether to obtain the product.

The present invention provides a method and idea for preparing an S-alkynyl functionalized reagent using a microchannel reactor. There are many methods and approaches to implement the technical solution. The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be considered as the scope of protection of the present invention. All components not specified in this embodiment can be implemented using existing technologies.

Claims (10)

1. a kind of method that utilizes microchannel reaction device to prepare S-diazoalkanes compound, it is characterized in that, will contain the first reaction liquid of sulfoxide compound and diazonium compound, and the first reaction solution containing trifluoromethanesulfonic anhydride The second reaction solution is reacted in the microchannel reaction device to obtain a reaction solution containing S-diazoalkane compounds; The sulfoxide compound is any one of the following compounds;

The diazo compound is ethyl diazoacetate and/or benzyl 2-diazoacetate; The S-diazoalkane compound is any one of the following compounds;

2. The method according to claim 1, wherein the solvent of the first reaction solution and the solvent of the second reaction solution are independently selected from dichloromethane, acetone, 1,2-dichloroethane, Acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide or a combination thereof. 3. The method according to claim 1, characterized in that the concentration of the sulfoxide compound in the first reaction solution is 0.2-2.5 mmol/mL. 4. The method according to claim 1, characterized in that the molar ratio of the sulfoxide compound to the diazo compound is 1:(1-5). 5. The method according to claim 1, characterized in that the molar ratio of the sulfoxide compound to trifluoromethanesulfonic anhydride is 1:(1-5). 6. The method according to claim 1, characterized in that the concentration of trifluoromethanesulfonic anhydride in the second reaction solution is 0.04˜3 mmol/mL. 7. The method according to claim 1, characterized in that, the inner diameter of the microchannel reactor in the microchannel reaction device is 0.5 to 1.0 mm. 8. The method according to claim 1, characterized in that, the length of the microchannel reactor in the microchannel reaction device is 5-20m. 9. The method according to claim 1, characterized in that the pumping rate ratio of the first reaction liquid and the second reaction liquid is 1:(0.5-1.5). 10. The method according to claim 1, characterized in that the reaction temperature is -50-30°C.

Images