CN114213299A - 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 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 (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 also 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 micro-flow field reaction technology is only reported, and a Togni alkynyl reagent is a common alkynylation reagent, but the synthesis process is complicated, and can be obtained by synthesis only through 3-4 steps of reaction, and the reaction process needs harsh reaction conditions such as strong alkali, ultralow temperature and the like, 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) (angew.chem.int.ed.,2018,57, 12538-. The method also requires harsh reaction conditions such as strong alkali, ultralow temperature and the like. 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 catalyst-free and additive-free alkynyl functional reagent which is environment-friendly is very meaningful.
Disclosure of Invention
The purpose of the invention is as follows: 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 problems, 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 a 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 content of the first and second substances,
R1selected from-H, methyl or halogen (-F, -Cl, -Br), preferably-H;
R2the compound is selected from alkyl, cycloalkyl, alkyl derivatives, heterocyclic compounds, aryl or aryl derivatives, preferably alkyl derivatives, aryl or aryl derivatives, and more preferably any one 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 method 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 method 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 method can directly realize the synthesis of the S-alkynyl functional compound by using the terminal alkyne, does not need to synthesize the alkyne into the midbody of the TMS-alkyne, and reduces the synthesis steps and the preparation cost.
(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 S- (4-tert-butylphenyl) ethynyl-S-diphenyltrifluoromethanesulfonate sulfonium salt.
FIG. 10 shows 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 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 diphenylsulfoxide was 90%. As shown in fig. 2, 3, and 4, the characterization data are as follows:1H 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).13C 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 C20H15S+[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), the pumping flow rate was 0.2mL/min, the reaction was carried out at 0 ℃ and the residence time was 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 3.75g of a final product, yield 86%, and conversion of diphenylsulfoxide was 94%.
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 and dissolved in acetonitrile 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, 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 diphenylsulfoxide was 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 is clear from Table 1, the reaction temperature has a great influence on the reaction yield, and the reaction yield increases as the reaction temperature increases, 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., dichloromethane as 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 dichloromethane 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 Effect 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 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 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:1H 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).13C 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),116.8,111.0,66.0,20.8.19F NMR(376MHz,Chloroform-d)δ78.10.HRMS(ESI)m/z:calcd for C21H17S+[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:1H 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).13C NMR(100MHz,Chloroform-d)δ157.6,134.9,133.7,131.8,129.5,128.1,126.3,121.(q,J＝318.6Hz,1C),113.7,112.4,62.2,35.5,30.9.19F NMR(376MHz,Chloroform-d)δ78.09.HRMS(ESI)m/z:calcd for C24H23S+[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), the pumping flow rate was 0.2mL/min, and the reaction was carried out at room temperature for 7.0 min. After the reaction is finished, TLC detection is carried out, and reduced pressure distillation is carried outThe solvent was removed and recovered, and column chromatography (dichloromethane: methanol ═ 30: 1) was performed to give 4.23g of the final product, yield 82%, and conversion of diphenyl sulfoxide 90%. As shown in fig. 11, 12, and 13, the characterization data are as follows:1H 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).13C NMR(100MHz,Chloroform-d)δ135.1,131.9,129.4,127.5,122.7,120.8(q,J＝318.6Hz,1C),18.4,11.0.19F NMR(376MHz,Chloroform-d)δ78.19.HRMS(ESI)m/z:calcd for C23H31SiS+[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 micro-channel and non-micro-channel 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]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]Reaction conditions are as follows: 2.02g (10.0mmol,1.0equiv) of diphenylsulfoxide was weighed out and dissolved in dichloro-methaneIn methane, the reaction solution was placed at-50 ℃ and low temperature, 2.02mL of trifluoromethanesulfonic anhydride (12.0mmol, 1.2equiv) was slowly added dropwise and reacted at-50 ℃ for 1 h; weighing alkyne (10.0mmol,1.0equiv), dissolving with 10mL dichloromethane, dropwise adding into a reaction system, slowly heating 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 (10)
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 the S-alkynyl functional compound shown in the formula I;
wherein the content of the first and second substances,
R1selected from-H, methyl or halogen;
R2selected from alkyl, cycloalkyl, alkyl derivatives, heterocycles, aryl or aryl derivatives.
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 the molar concentration of the diphenyl sulfoxide compound in the step (1) 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).
10. The method according to claim 1, wherein the reaction temperature is-50 to 30 ℃.
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| BERND WALDECKER，等: "5-(Alkynyl)dibenzothiophenium Triflates: Sulfur-Based Reagents for Electrophilic Alkynylation", 《ANGEW. CHEM. INT. ED.》 * |
| LONG-ZHOU QIN，等: "Continuous-flow processes for the S-alkynylation of cysteine-containing peptides and thioglycosides under catalyst-free, oxidant-free and mild conditions", 《GREEN CHEM.》 * |
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