CN114213299B - Method for preparing S-alkynyl functionalized compound by using microchannel reaction device - Google Patents
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Abstract
The invention discloses a method for preparing an S-alkynyl functionalized compound by using a microchannel reaction device, which comprises the following steps: (1) dissolving diphenyl sulfoxide compound shown as formula II and alkyne compound shown as formula III in solvent as first reactionSolution reaction; (2) dissolving trifluoromethanesulfonic anhydride in a solvent to obtain a second reaction solution; (3) and (3) reacting the first reaction solution and the second reaction solution in a microchannel reactor to obtain the reaction solution containing the S-alkynyl functional compound shown in the formula I. The reaction involved in the invention is a brand-new method for synthesizing the S-alkynylation reagent, can be carried out at room temperature, does not need to add a catalyst or other additives, overcomes the harsh conditions of the traditional synthetic method, and has good amplification prospect.
Description
Technical Field
The invention belongs to the field of chemical synthesis, and particularly relates to a method for preparing an S-alkynyl functionalized compound by using a microchannel reaction device.
Background
Alkyne compounds are important pharmaceutical and chemical intermediates, and are widely applied to the fields of modern organic synthesis, pharmaceutical chemistry, material science and the like. Therefore, the synthesis of alkynyl functional reagents has received a great deal of attention from chemists.
The traditional chemical reaction process is more intermittent, the reaction and separation efficiency is not high, the pollutant emission is serious, the process route is overlong, and safety accidents are easily caused by improper operation, so that the green intelligent development process of chemical production is seriously hindered. The micro-flow field reaction technology is a process strengthening technology with the characteristic dimension of reaction and dispersion in hundreds of microns. The technology builds a desktop factory for the traditional chemical industry, and points out the direction for the green development of the chemical industry.
At present, a method for synthesizing an S-alkynylation reagent by using a microfluidic reaction technology is rarely reported, and a Togni alkynyl reagent is a common alkynylation reagent, but the synthesis process is complicated, and needs 3 to 4 steps of reaction to obtain the reagent, and the reaction process needs harsh reaction conditions such as strong alkali and ultralow temperature, so that safety accidents are easily caused by improper operation (j.am.chem.soc.,2014,136, 16563-. The Manuel Alcarazo topic group reported in 2018 a method for the synthesis of 5- (alkynyl) dibenzothiophene triflate (Umemoto alkynyl reagent) (angelw.chem.int.ed., 2018,57, 12538-. The method also requires harsh reaction conditions such as strong alkali and ultralow temperature. The traditional preparation method of the alkynyl functional reagent has the defects of multiple synthesis steps, serious energy waste, environmental friendliness and the like, and the defects limit the application of the alkynyl functional reagent in industrialization, so that the development of a preparation method of the alkynyl functional reagent which is free of a catalyst and an additive and is environment-friendly is very meaningful.
Disclosure of Invention
The invention aims to: the technical problem to be solved by the invention is to provide a method for preparing an S-alkynyl functionalized compound by using a microchannel reaction device, aiming at the defects of the prior art.
In order to solve the technical problem, the invention discloses a method for preparing an S-alkynyl functionalized compound by using a microchannel reaction device, which comprises the following steps:
(1) dissolving a diphenyl sulfoxide compound shown in a formula II and an alkyne compound shown in a formula III in a solvent to obtain a first reaction solution;
(2) dissolving trifluoromethanesulfonic anhydride in a solvent to obtain a second reaction solution;
(3) and respectively pumping the first reaction liquid and the second reaction liquid into the microchannel reactor simultaneously for reaction, collecting effluent liquid to obtain reaction liquid containing the S-alkynyl functional compound shown in the formula I, and performing post treatment to obtain the S-alkynyl functional compound.
Wherein, the first and the second end of the pipe are connected with each other,
R 1 selected from-H, methyl or halogen (-F, -Cl, -Br), preferably-H;
R 2 selected from alkyl, cycloalkyl, alkyl derivatives, heterocycles, aryl or aryl derivatives, preferablyIs an alkyl derivative, an aryl group or an aryl derivative, and is more preferably any of phenyl, o-methylphenyl, 4-tert-butylphenyl and triisopropylsilyl.
Among them, the diphenyl sulfoxide compound represented by the formula II is preferably diphenyl sulfoxide.
Wherein, the alkyne compound shown in the formula III is preferably any one or a combination of a plurality of phenylacetylene, o-tolylacetylene, 4-tert-butyl phenylacetylene and triisopropyl silylethynylene.
The solvent in the step (1) and the solvent in the step (2) are respectively and independently selected from dichloromethane, acetone, 1, 2-dichloroethane, acetonitrile, N-dimethylformamide, N-dimethylacetamide, tetrahydrofuran, dimethyl sulfoxide or a plurality of combinations thereof.
In the step (1), the molar concentration of the diphenyl sulfoxide compound is 0.2-2.0 mmol/L, and preferably 1.0 mmol/L.
In the step (1), the molar ratio of the diphenyl sulfoxide compound to the alkyne compound is 1 (1-5), and preferably 1 (1-2).
Wherein the molar ratio of the diphenyl sulfoxide compound to the trifluoromethanesulfonic anhydride is 1 (1-5), and preferably 1 (1-2.5).
In the step (2), the concentration of the trifluoromethanesulfonic anhydride is 0.8-1.6 mmol/mL, and preferably 1.2 mmol/mL.
In the step (3), the microchannel reactor device comprises a feeding pump (bagging Leifu Fluid Technology co.ltd, (TYD01-01-CE type)), a mixing module, a microchannel reactor and a receiver; wherein, the feed pump is connected with the mixing module, the micro-channel reactor and the receiver in series through pipelines in turn, as shown in figure 1.
The microchannel reactor is of a pore channel structure, the number of pore channels is increased or reduced according to needs, and the pore channel material is polytetrafluoroethylene or perfluoroalkoxy alkane (PFA).
The inner diameter of the microchannel reactor is 0.5-1.0 mm, and preferably 0.6 mm.
Wherein the length of the microchannel reactor is 5-20 m.
The volume of the microchannel reactor is 1-15.7 mL, and 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), and preferably 1: 1.
In the step (3), the pumping rates of the first reaction liquid and the second reaction liquid are both 0.1-5.0 mL/min.
In the step (3), the reaction temperature is controlled to be-50-30 ℃, preferably-20-30 ℃, and further preferably room temperature.
In the step (3), the reaction time is 30s to 2.6h, preferably 5min to 60min, more preferably 5min to 30min, further preferably 5min to 10min, and most preferably 7 min.
Has the advantages that: compared with the prior art, the invention has the following advantages:
(1) the new compound structure is synthesized, and the reagent can be prepared by reacting diphenyl sulfoxide, terminal alkyne and trifluoromethanesulfonic anhydride in a microchannel reactor.
(2) The reaction operation is simple, the experimental steps are reduced, the dropping process of the trifluoromethanesulfonic anhydride is avoided, the safety is high, the defects of the traditional method are overcome, the reaction time is shortened, the reaction conversion rate and the yield are improved, and the reaction continuity is high, so that continuous uninterrupted amplification production is facilitated.
(3) The invention can synthesize the S-alkynyl functional compound at room temperature, overcomes the harsh conditions of ultralow temperature in the prior art, and reduces energy consumption and production cost.
(4) The invention does not need to add any additive, avoids the use of strong alkali, reduces the steps of post-treatment and the discharge of wastes, and is beneficial to the application to industrial scale-up production.
(5) The synthesis of the S-alkynyl functional compound can be directly realized by using the terminal alkyne, and the alkyne does not need to be synthesized into the midbody of TMS-alkyne, so that the synthesis steps and the preparation cost are reduced.
(6) The product conversion rate of the invention is 84-97%, and the yield is up to 78-93%.
Drawings
FIG. 1 is a schematic diagram of the reaction scheme of the present invention.
FIG. 2 shows a hydrogen spectrum of a sulfonium S- (phenyl) ethynyl-S-diphenyltrifluoromethanesulfonate.
FIG. 3 is a carbon spectrum diagram of a sulfonium S- (phenyl) ethynyl-S-diphenyltrifluoromethanesulfonate.
FIG. 4 is a fluorine spectrum of a sulfonium S- (phenyl) ethynyl-S-diphenyltrifluoromethanesulfonate.
FIG. 5 is a hydrogen spectrum diagram of a sulfonium S- (2-methylphenyl) ethynyl-S-diphenyltrifluoromethanesulfonate.
FIG. 6 is a carbon spectrum diagram of S- (2-methylphenyl) ethynyl-S-diphenyl trifluoromethanesulfonic acid sulfonium salt.
FIG. 7 shows a fluorine spectrum of a sulfonium S- (2-methylphenyl) ethynyl-S-diphenyltrifluoromethanesulfonate.
FIG. 8 is a hydrogen spectrum diagram of a sulfonium S- (4-tert-butylphenyl) ethynyl-S-diphenyltrifluoromethanesulfonate.
FIG. 9 is a carbon spectrum diagram of a sulfonium S- (4-tert-butylphenyl) ethynyl-S-diphenyltrifluoromethanesulfonate.
FIG. 10 is a fluorine spectrum of a sulfonium S- (4-tert-butylphenyl) ethynyl-S-diphenyltrifluoromethanesulfonate.
FIG. 11 is a hydrogen spectrum of a sulfonium S- (triisopropylsilyl) ethynyl-S-diphenyltrifluoromethanesulfonate.
FIG. 12 is a carbon spectrum diagram of S- (triisopropylsilyl) ethynyl-S-diphenyl trifluoromethanesulfonic acid sulfonium salt.
FIG. 13 is a fluorine spectrum of the sulfonium S- (triisopropylsilyl) ethynyl-S-diphenyltrifluoromethanesulfonate.
Detailed Description
The invention will be better understood from the following examples. However, those skilled in the art will readily appreciate that the description of the embodiments is only for illustrating the present invention and should not be taken as limiting the invention as detailed in the claims.
Example 1
2.02g (10.0mmol,1.0equiv) of diphenylsulfoxide and 1.02g (10.0mmol,1.0equiv) of phenylacetylene were weighed out and dissolved in dichloromethane to prepare a 10.0mL solution as a first reaction solution. 2.02mL of trifluoromethanesulfonic anhydride (12.0mmol, 1.2equiv) was weighed out and dissolved in methylene chloride to prepare a 10.0mL solution as a second reaction solution. The first reaction solution and the second reaction solution were simultaneously pumped into a microchannel reactor (inner diameter 0.6mm, volume 2.8mL), the pumping flow rate was 0.2mL/min, and the reaction was carried out at-20 ℃ for a residence time of 7.0 min. After the completion of the reaction, TLC was carried out, and the solvent was removed by distillation under reduced pressure and recovered, and column chromatography (dichloromethane: methanol: 30: 1) was carried out to obtain 3.57g of a final product, yield 82%, and conversion of diphenyl sulfoxide was 90%. As shown in fig. 2, 3, and 4, the characterization data are as follows: 1 H NMR(400MHz,Chloroform-d)δ8.22–8.16(m,4H),7.82–7.78(m,2H),7.76–7.67(m,7H),7.64–7.59(m,1H),7.49(t,J＝7.7Hz,2H). 13 C NMR(100MHz,Chloroform-d)δ134.9,133.7,133.3,131.9,129.6,129.2,127.9,116.9,111.4,63.0.HRMS(ESI)m/z:calcd for C 20 H 15 S + [M–OTf] + :287.0889,found:287.0892.
example 2
2.02g (10.0mmol,1.0equiv) of diphenylsulfoxide and 1.02g (10.0mmol,1.0equiv) of phenylacetylene were weighed out and dissolved in dichloromethane to prepare a 10.0mL solution as a first reaction solution. 2.02mL of trifluoromethanesulfonic anhydride (12.0mmol, 1.2equiv) was weighed out and dissolved in methylene chloride to prepare a 10.0mL solution as a second reaction solution. The first reaction solution and the second reaction solution were simultaneously pumped into a microchannel reactor (inner diameter 0.6mm, volume 2.8mL) at a flow rate of 0.2mL/min, and reacted at 0 ℃ for a residence time of 7.0 min. After the completion of the reaction, TLC was carried out, and the solvent was removed by distillation under reduced pressure and recovered, and the final product was obtained by column chromatography (dichloromethane: methanol: 30: 1) in 3.75g, 86% yield and 94% conversion of diphenyl sulfoxide.
Example 3
2.02g (10.0mmol,1.0equiv) of diphenylsulfoxide and 1.02g (10.0mmol,1.0equiv) of phenylacetylene were weighed out and dissolved in dichloromethane to prepare a 10.0mL solution as a first reaction solution. 2.02mL of trifluoromethanesulfonic anhydride (12.0mmol, 1.2equiv) was weighed out and dissolved in methylene chloride to prepare a 10.0mL solution as a second reaction solution. The first reaction solution and the second reaction solution were simultaneously pumped into a microchannel reactor (inner diameter 0.6mm, volume 2.8mL), the pumping flow rate was 0.2mL/min, and the reaction was carried out at room temperature for 7.0 min. After completion of the reaction, TLC was carried out, the solvent was removed by distillation under reduced pressure and recovered, and column chromatography (dichloromethane: methanol: 30: 1) was carried out to obtain 4.01g of a final product, yield 92%, and conversion of diphenyl sulfoxide 96%.
Example 4
2.02g (10.0mmol,1.0equiv) of diphenylsulfoxide and 1.02g (10.0mmol,1.0equiv) of phenylacetylene were weighed and dissolved in 1, 2-dichloroethane to prepare a 10mL solution as a first reaction solution. 2.02mL of trifluoromethanesulfonic anhydride (12.0mmol, 1.2equiv) was weighed out and dissolved in 1, 2-dichloroethane to prepare a 10mL solution as a second reaction solution. The first reaction solution and the second reaction solution were simultaneously pumped into a microchannel reactor (inner diameter 0.6mm, volume 2.8mL), the pumping flow rate was 0.2mL/min, and the reaction was carried out at room temperature for 7.0 min. After completion of the reaction, TLC was carried out, and the solvent was removed by distillation under reduced pressure and recovered, and column chromatography (dichloromethane: methanol: 30: 1) was carried out to obtain 3.70g of a final product, yield 85%, and conversion of diphenylsulfoxide 92%.
Example 5
2.02g (10.0mmol,1.0equiv) of diphenylsulfoxide and 1.02g (10.0mmol,1.0equiv) of phenylacetylene were weighed and dissolved in acetonitrile to prepare a 10.0mL solution as a first reaction solution. 2.02mL of trifluoromethanesulfonic anhydride (12.0mmol, 1.2equiv) was weighed out, dissolved in acetonitrile, and prepared into a 10.0mL solution as a second reaction solution. The first reaction solution and the second reaction solution were simultaneously pumped into a microchannel reactor (inner diameter 0.6mm, volume 2.8mL) at a flow rate of 0.2mL/min, and reacted at room temperature for a residence time of 7.0 min. After the completion of the reaction, TLC was carried out, and the solvent was removed by distillation under reduced pressure and recovered, and column chromatography (dichloromethane: methanol: 30: 1) was carried out to obtain 3.49g of a final product, yield 80%, and conversion of diphenyl sulfoxide 90%.
Example 6
2.02g (10.0mmol,1.0equiv) of diphenylsulfoxide and 1.02g (10.0mmol,1.0equiv) of phenylacetylene were weighed out and dissolved in dichloromethane to prepare a 10.0mL solution as a first reaction solution. 2.02mL of trifluoromethanesulfonic anhydride (12.0mmol, 1.2equiv) was weighed out and dissolved in methylene chloride to prepare a 10.0mL solution as a second reaction solution. The first reaction solution and the second reaction solution were simultaneously pumped into a microchannel reactor (inner diameter 0.6mm, volume 2.8mL), the pumping flow rate was 0.4mL/min, and the reaction was carried out at room temperature for 3.5 min. After completion of the reaction, TLC was carried out, the solvent was removed by distillation under reduced pressure and recovered, and column chromatography (dichloromethane: methanol: 30: 1) was carried out to obtain 3.40g of a final product, yield 78%, and conversion of diphenylsulfoxide was 84%.
Example 7
2.02g (10.0mmol,1.0equiv) of diphenylsulfoxide and 1.02g (10.0mmol,1.0equiv) of phenylacetylene were weighed out and dissolved in dichloromethane to prepare a 10.0mL solution as a first reaction solution. 2.02mL of trifluoromethanesulfonic anhydride (12.0mmol, 1.2equiv) was weighed out and dissolved in methylene chloride to prepare a 10.0mL solution as a second reaction solution. The first reaction solution and the second reaction solution were simultaneously pumped into a microchannel reactor (inner diameter 0.6mm, volume 2.8mL), the pumping flow rate was 0.1mL/min, and the reaction was carried out at room temperature for 14.0 min. After completion of the reaction, TLC was carried out, and the solvent was removed by distillation under reduced pressure and recovered, and column chromatography (dichloromethane: methanol ═ 30: 1) was carried out to obtain 4.05g of the final product, yield 93%, and conversion of diphenyl sulfoxide was 97%.
The advantages of the process of the invention are illustrated by the above experiments:
1. to examine the effect of the reaction temperature on the reaction yield, in example 1 (i.e., methylene chloride as a solvent, a feed flow rate of 0.2mL/min, a residence time of 7.0min, a reaction temperature of-20 ℃ C.). On the basis, different reaction temperatures are respectively adopted, and the influence of the reaction temperatures on the yield is further investigated. The specific settings are as follows: example 2 the reaction temperature used was 0 ℃; example 3 the reaction temperature was room temperature; the comparison results are shown in table 1.
TABLE 1 Effect of different reaction temperatures on the reaction yield
| Experimental group | Reaction temperature (. degree.C.) | Yield (%) |
| Example 1 | -20 | 82 |
| Example 2 | 0 | 86 |
| Example 3 | At room temperature | 92 |
As can be seen from Table 1, the reaction temperature has a great influence on the reaction yield, and the reaction yield increases with the increase of the reaction temperature, and the reaction yield can reach 92% at room temperature, and the reaction temperature is set to room temperature in order to reduce energy consumption.
2. To examine the effect of the reaction solvent on the reaction yield, in example 3 (i.e., methylene chloride as the solvent, feed flow rate of 0.2mL/min, residence time of 7.0min, reaction temperature of room temperature). On the basis, different reaction solvents are respectively adopted, and the influence of the reaction solvents on the yield is further investigated. The specific settings are as follows: example 4 the reaction solvent used was 1, 2-dichloroethane; example 5 the reaction solvent used was acetonitrile; the comparison results are shown in table 2.
TABLE 2 Effect of different reaction solvents on the reaction yield
| Experimental group | Solvent(s) | Yield (%) |
| Example 3 | Methylene dichloride | 92 |
| Example 4 | 1, 2-dichloroethane | 85 |
| Example 5 | |
80 |
As can be seen from table 2, different reaction solvents have a great influence on the reaction yield, and the highest reaction yield can be obtained when methylene chloride is used as the reaction solvent.
3. To examine the effect of residence time on reaction yield, in example 3 (i.e., dichloromethane as solvent, feed flow rate of 0.2mL/min, residence time of 7.0min, reaction temperature of room temperature). On the basis, different residence times are adopted, and the influence of the residence time on the reaction yield is further examined. The specific settings are as follows: example 6 the residence time used was 3.5 min; example 7 used a residence time of 14.0 min. The comparison results are shown in table 3.
TABLE 3 influence of different residence times on the reaction yield
| Experimental group | Residence time (min) | Yield (%) |
| Example 3 | 7.0 | 92 |
| Example 6 | 3.5 | 78 |
| Example 7 | 14.0 | 93 |
As is clear from table 3, the residence time of the reaction greatly affects the reaction yield, and when the time is too short, the amount of the raw materials remaining is large, the reaction yield is low, and the reaction yield increases with the increase of the residence time, but the residence time exceeds 7.0min, and the increase of the reaction yield is not significant due to the increase of the residence time, so that 7.0min is selected as the optimum residence time.
Example 8
2.02g (10.0mmol,1.0equiv) of diphenylsulfoxide and 1.16g (10.0mmol,1.0equiv) of o-tolylacetylene were weighed out and dissolved in methylene chloride to prepare a 10.0mL solution as a first reaction solution. 2.02mL of trifluoromethanesulfonic anhydride (12.0mmol, 1.2equiv) was measured and dissolved in methylene chloride to prepare a 10.0mL solution as the second solutionAnd (2) reacting liquid. The first reaction solution and the second reaction solution were simultaneously pumped into a microchannel reactor (inner diameter 0.6mm, volume 2.8mL) at a flow rate of 0.2mL/min, and reacted at room temperature for a residence time of 7.0 min. After completion of the reaction, TLC was carried out, the solvent was removed by distillation under reduced pressure and recovered, and column chromatography (dichloromethane: methanol: 30: 1) was carried out to obtain 3.96g of a final product, yield 88%, and conversion of diphenylsulfoxide was 96%. As shown in fig. 5, 6, and 7, the characterization data are as follows: 1 H NMR(400MHz,Chloroform-d)δ8.25–8.17(m,4H),7.79–7.69(m,7H),7.50(t,J＝7.3Hz,1H),7.35–7.28(m,2H),2.52(s,3H). 13 C NMR(100MHz,Chloroform-d)δ143.4,135.0,134.5,133.3,131.9,130.4,129.5,128.0,126.6,120.9(q,J＝318.9Hz,1C),116.8,111.0,66.0,20.8. 19 F NMR(376MHz,Chloroform-d)δ78.10.HRMS(ESI)m/z:calcd for C 21 H 17 S + [M–OTf] + :301.1045,found:301.1041.
example 9
2.02g (10.0mmol,1.0equiv) of diphenylsulfoxide and 1.58g (10.0mmol,1.0equiv) of 4-tert-butylacetylene were weighed and dissolved in dichloromethane to prepare a 10.0mL solution as a first reaction solution. 2.02mL of trifluoromethanesulfonic anhydride (12.0mmol, 1.2equiv) was weighed out and dissolved in methylene chloride to prepare a 10.0mL solution as a second reaction solution. The first reaction solution and the second reaction solution were simultaneously pumped into a microchannel reactor (inner diameter 0.6mm, volume 2.8mL), the pumping flow rate was 0.2mL/min, and the reaction was carried out at room temperature for 7.0 min. After completion of the reaction, TLC was carried out, the solvent was removed by distillation under reduced pressure and recovered, and column chromatography (dichloromethane: methanol ═ 30: 1) was carried out to obtain 4.23g of the final product, yield 86%, and conversion of diphenylsulfoxide was 95%. As shown in fig. 8, 9, and 10, the characterization data are as follows: 1 H NMR(400MHz,Chloroform-d)δ8.27–8.14(m,4H),7.78–7.67(m,8H),7.51(d,J＝8.5Hz,2H),1.32(s,9H). 13 C NMR(100MHz,Chloroform-d)δ157.6,134.9,133.7,131.8,129.5,128.1,126.3,121.(q,J＝318.6Hz,1C),113.7,112.4,62.2,35.5,30.9. 19 F NMR(376MHz,Chloroform-d)δ78.09.HRMS(ESI)m/z:calcd for C 24 H 23 S + [M–OTf] + :343.1515,found:343.1519.
example 10
2.02g (10.0mmol,1.0equiv) of diphenylsulfoxide and 1.82g (10.0mmol,1.0equiv) of triisopropylsilylacetylene were weighed out and dissolved in methylene chloride to prepare a 10.0mL solution as a first reaction solution. 2.02mL of trifluoromethanesulfonic anhydride (12.0mmol, 1.2equiv) was weighed out and dissolved in methylene chloride to prepare a 10.0mL solution as a second reaction solution. The first reaction solution and the second reaction solution were simultaneously pumped into a microchannel reactor (inner diameter 0.6mm, volume 2.8mL) at a flow rate of 0.2mL/min, and reacted at room temperature for a residence time of 7.0 min. After completion of the reaction, TLC was carried out, the solvent was removed by distillation under reduced pressure and recovered, and column chromatography (dichloromethane: methanol ═ 30: 1) was carried out to obtain 4.23g of the final product, yield 82%, and conversion of diphenylsulfoxide was 90%. As shown in fig. 11, 12, and 13, the characterization data are as follows: 1 H NMR(400MHz,Chloroform-d)δ8.17–8.12(m,4H),7.77–7.69(m,6H),1.32–1.25(m,3H),1.14(d,J＝7.2Hz,18H). 13 C NMR(100MHz,Chloroform-d)δ135.1,131.9,129.4,127.5,122.7,120.8(q,J＝318.6Hz,1C),18.4,11.0. 19 F NMR(376MHz,Chloroform-d)δ78.19.HRMS(ESI)m/z:calcd for C 23 H 31 SiS + [M–OTf] + :367.1910,found:367.1910.
comparative example 1
Weighing 2.02g (10.0mmol,1.0equiv) of diphenyl sulfoxide, dissolving the diphenyl sulfoxide in dichloromethane, slowly adding 2.02mL of trifluoromethanesulfonic anhydride (12.0mmol, 1.2equiv) dropwise at the low temperature of-50 ℃, and reacting for 1h at-50 ℃; weighing 1.02g (10.0mmol,1.0equiv) of phenylacetylene, dissolving with 10mL of dichloromethane, dropwise adding into a reaction system, slowly heating the reaction temperature to-15 ℃ and continuing to react for 5h, performing TLC detection after the reaction is finished, removing the solvent by reduced pressure distillation and recovering, and obtaining 3.62g of a final product by column chromatography (dichloromethane: methanol is 30: 1), wherein the yield is 83%, and the conversion rate of the diphenyl sulfoxide is 90%.
Comparative examples 2 to 4
Referring to comparative example 1 above, alkynes were replaced with the alkynes in examples 8 to 10, respectively, and the results are shown in Table 4.
TABLE 4 yield of product obtained in microchannel and non-microchannel environments for different alkynes
| Examples | Alkynes of acetylene | Yield of [a] (％) | Yield of [b] (％) |
| 3 | Phenylacetylene | 92 | 83 |
| 8 | O-methyl phenylacetylene | 88 | 80 |
| 9 | 4-tert-butyl phenylacetylene | 86 | 80 |
| 10 | Tri-isopropyl silyl acetylene | 82 | 75 |
[a] The reaction conditions are as follows: diphenylsulfoxide (10.0mmol,1.0equiv) and alkyne (10.0mmol,1.0equiv) were weighed out and dissolved in dichloromethane to prepare a 10mL solution, and 2.02mL of trifluoromethanesulfonic anhydride (12.0mmol, 1.2equiv) was weighed out as a first reaction solution and dissolved in dichloromethane to prepare a 10mL solution as a second reaction solution. The first reaction solution and the second reaction solution were simultaneously pumped into a microchannel reactor (inner diameter 0.6mm, volume 2.8mL), the pumping flow rate was 0.2mL/min, and the reaction was carried out at room temperature for 7.0 min. And (3) after the reaction is finished, performing TLC detection, distilling under reduced pressure to remove the solvent and recovering, and performing column chromatography to obtain the product.
[b] The reaction conditions are as follows: weighing 2.02g (10.0mmol,1.0equiv) of diphenyl sulfoxide, dissolving the diphenyl sulfoxide in dichloromethane, slowly adding 2.02mL of trifluoromethanesulfonic anhydride (12.0mmol, 1.2equiv) dropwise at the low temperature of-50 ℃, and reacting for 1h at-50 ℃; weighing alkyne (10.0mmol,1.0equiv), dissolving with 10mL dichloromethane, dropwise adding into a reaction system, slowly heating the reaction temperature to-15 ℃, continuing to react for 5 hours, carrying out TLC detection after the reaction is finished, distilling under reduced pressure to remove the solvent, recovering, and carrying out column chromatography to obtain the product.
The present invention provides a method and a concept for preparing S-alkynyl functionalized compounds using a microchannel reactor, and a method and a way for implementing the technical scheme are numerous, and the above description is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, a plurality of modifications and embellishments can be made without departing from the principle of the present invention, and these modifications and embellishments should also 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.
Claims (9)
1. A method for preparing an S-alkynyl functionalized compound by using a microchannel reaction device is characterized by comprising the following steps:
(1) dissolving a diphenyl sulfoxide compound shown in a formula II and an alkyne compound shown in a formula III in a solvent to obtain a first reaction solution;
(2) dissolving trifluoromethanesulfonic anhydride in a solvent to obtain a second reaction solution;
(3) reacting the first reaction solution and the second reaction solution in a microchannel reactor to obtain a reaction solution containing an S-alkynyl functional compound shown in a formula I;
wherein the content of the first and second substances,
R 1 is selected from-H;
R 2 selected from phenyl, o-methylphenyl, 4-tert-butylphenyl or triisopropylsilyl;
the reaction temperature is-20-30 ℃; the reaction residence time is 5min to 30 min.
2. The process of claim 1, wherein the solvent in step (1) and the solvent in step (2) are each independently selected from the group consisting of dichloromethane, acetone, 1, 2-dichloroethane, acetonitrile, N-dimethylformamide, N-dimethylacetamide, tetrahydrofuran, dimethylsulfoxide, and combinations thereof.
3. The method according to claim 1, wherein in the step (1), the molar concentration of the diphenyl sulfoxide compound is 0.2-2.0 mmol/L.
4. The method according to claim 1, wherein in the step (1), the molar ratio of the diphenyl sulfoxide compound to the alkyne compound is 1 (1-5).
5. The method according to claim 1, wherein the molar ratio of the diphenyl sulfoxide compound to the trifluoromethanesulfonic anhydride is 1 (1-5).
6. The method according to claim 1, wherein the concentration of the trifluoromethanesulfonic anhydride in step (2) is 0.8 to 1.6 mmol/mL.
7. The method of claim 1, wherein in step (3), the inner diameter of the microchannel reactor in the microchannel reactor device is 0.5-2.0 mm.
8. The method of claim 1, wherein in step (3), the length of the microchannel reactor in the microchannel reactor device is 5-20 m.
9. The method according to claim 1, wherein the pumping rate ratio of the first reaction solution to the second reaction solution is 1 (0.5-1.5).
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