CN114315793B - Method for preparing S-diazoalkane compound by utilizing micro-channel reaction device - Google Patents
Method for preparing S-diazoalkane compound by utilizing micro-channel reaction device Download PDFInfo
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- 238000006243 chemical reaction Methods 0.000 title claims abstract description 102
- 238000000034 method Methods 0.000 title claims abstract description 32
- 150000001875 compounds Chemical class 0.000 title claims abstract description 20
- 239000012295 chemical reaction liquid Substances 0.000 claims abstract description 53
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 claims abstract description 42
- -1 sulfoxide compounds Chemical class 0.000 claims abstract description 14
- 150000008049 diazo compounds Chemical class 0.000 claims abstract 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 113
- 239000002904 solvent Substances 0.000 claims description 18
- 238000005086 pumping Methods 0.000 claims description 14
- YVPJCJLMRRTDMQ-UHFFFAOYSA-N ethyl diazoacetate Chemical compound CCOC(=O)C=[N+]=[N-] YVPJCJLMRRTDMQ-UHFFFAOYSA-N 0.000 claims description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- 150000001989 diazonium salts Chemical class 0.000 claims description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 4
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 2
- 238000003786 synthesis reaction Methods 0.000 abstract description 10
- 230000015572 biosynthetic process Effects 0.000 abstract description 9
- 230000002194 synthesizing effect Effects 0.000 abstract description 4
- 239000000243 solution Substances 0.000 description 48
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 39
- 239000000047 product Substances 0.000 description 27
- 238000001228 spectrum Methods 0.000 description 21
- 238000005481 NMR spectroscopy Methods 0.000 description 17
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 11
- JJHHIJFTHRNPIK-UHFFFAOYSA-N Diphenyl sulfoxide Chemical compound C=1C=CC=CC=1S(=O)C1=CC=CC=C1 JJHHIJFTHRNPIK-UHFFFAOYSA-N 0.000 description 10
- 238000001514 detection method Methods 0.000 description 10
- 239000012467 final product Substances 0.000 description 10
- 238000004821 distillation Methods 0.000 description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 7
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 7
- 229910052799 carbon Inorganic materials 0.000 description 7
- 238000012512 characterization method Methods 0.000 description 7
- 229910052731 fluorine Inorganic materials 0.000 description 7
- 239000011737 fluorine Substances 0.000 description 7
- 229910052739 hydrogen Inorganic materials 0.000 description 7
- 239000001257 hydrogen Substances 0.000 description 7
- NGDPCAMPVQYGCW-UHFFFAOYSA-N dibenzothiophene 5-oxide Chemical compound C1=CC=C2S(=O)C3=CC=CC=C3C2=C1 NGDPCAMPVQYGCW-UHFFFAOYSA-N 0.000 description 5
- 238000005516 engineering process Methods 0.000 description 5
- 239000000758 substrate Substances 0.000 description 5
- 125000000217 alkyl group Chemical group 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 4
- 239000012954 diazonium Substances 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 238000005303 weighing Methods 0.000 description 3
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- FJNMYEBXFNFTBJ-UHFFFAOYSA-N Fc1cc2Sc3cc(F)c(F)cc3S(=O)c2cc1F Chemical compound Fc1cc2Sc3cc(F)c(F)cc3S(=O)c2cc1F FJNMYEBXFNFTBJ-UHFFFAOYSA-N 0.000 description 2
- 239000004813 Perfluoroalkoxy alkane Substances 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 229920011301 perfluoro alkoxyl alkane Polymers 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- NYVGTLXTOJKHJN-UHFFFAOYSA-N thianthrene 5-oxide Chemical compound C1=CC=C2S(=O)C3=CC=CC=C3SC2=C1 NYVGTLXTOJKHJN-UHFFFAOYSA-N 0.000 description 2
- KJGYFISADIZFEL-UHFFFAOYSA-N 1-chloro-4-(4-chlorophenyl)sulfinylbenzene Chemical compound C1=CC(Cl)=CC=C1S(=O)C1=CC=C(Cl)C=C1 KJGYFISADIZFEL-UHFFFAOYSA-N 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- 238000004293 19F NMR spectroscopy Methods 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 description 1
- JBBKWIFIXPBQGZ-UHFFFAOYSA-N 2-diazonio-1-phenylmethoxyethenolate Chemical compound [N-]=[N+]=CC(=O)OCC1=CC=CC=C1 JBBKWIFIXPBQGZ-UHFFFAOYSA-N 0.000 description 1
- TWGCGLQQMJASDN-UHFFFAOYSA-N 4-(benzenesulfonyl)-n-benzyl-5-chloro-1,3-thiazol-2-amine Chemical compound N=1C(S(=O)(=O)C=2C=CC=CC=2)=C(Cl)SC=1NCC1=CC=CC=C1 TWGCGLQQMJASDN-UHFFFAOYSA-N 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 238000012824 chemical production Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
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- 238000010586 diagram Methods 0.000 description 1
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- 239000003344 environmental pollutant Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical class I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 231100000719 pollutant Toxicity 0.000 description 1
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 1
- 239000004810 polytetrafluoroethylene Substances 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000013341 scale-up Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
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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
Technical Field
The invention belongs to the field of chemical synthesis, and particularly relates to a method for preparing S-diazoalkane compounds by using a micro-channel reaction device.
Background
The traditional chemical reaction process has the defects of intermittent type more reaction and separation efficiency, serious pollutant discharge, overlong process route and improper operation, and is easy to cause safety accidents, and the process seriously hinders the green intelligent development process of chemical production. The micro-flow field reaction technology is a process strengthening technology with the characteristic scale of reaction and dispersion in hundred micrometers. The technology builds a table top factory for traditional chemical industry, and simultaneously indicates the direction for the green development of the chemical industry.
At present, a method for synthesizing S-diazoalkane by utilizing a micro-flow field reaction technology is still rarely reported. In 2018, matthew J.Gaunt task group at Cambridge university reported a method for synthesizing a high-valent iodo-diazoalkane using (2, 4-difluorophenyl) -lambda 3 Iodinated diacetate and alpha-weightAzodicarbonyl compound is used as raw material to synthesize iodonium salt reagent of iodinated diazoalkane (Nature, 2018,562,563-568). In 2021, the Manuel Alcarazo group reported for the first time a method for synthesizing S-diazoalkane, which synthesized S-diazoalkane compounds (Angew.chem.int.ed.2021, 60, 6943-6948) in the form of triflate under ultra-low temperature conditions using sulfoxide compounds and ethyl diazoacetate as raw materials. Although the two methods successfully realize the synthesis of the target compound, the problems of harsh reaction conditions, small synthesis scale, low reaction yield and the like exist. Therefore, it is very interesting to develop a synthesis method of S-diazoalkane which is mild in reaction conditions, high in product yield and easy to scale up.
Disclosure of Invention
The invention aims to: the invention aims to solve the technical problem of providing a method for preparing S-diazoalkane compounds by utilizing a microchannel reaction device.
In order to solve the technical problems, the invention discloses a method for preparing S-diazonium alkane compounds by utilizing a microchannel reaction device, which comprises the steps of reacting a first reaction solution containing sulfoxide compounds shown in a formula II and diazonium compounds shown in a formula III with a second reaction solution containing trifluoro methanesulfonic anhydride in the microchannel reaction device, collecting effluent liquid, and obtaining the reaction solution containing S-diazonium alkane compounds shown in a formula I, and carrying out post treatment to obtain the S-diazonium alkane compounds.
Wherein,,
R 1 selected from-H, methyl or halogen (-F, -Cl, -Br), preferably-H, methyl or-Cl, further preferably-H;
R 2 selected from alkyl, alkyl derivatives, heterocyclic compounds, aryl or aryl derivatives, preferably alkyl or benzyl (Bn), more preferably alkyl, even more preferably-CH 2 CH 3 。
Wherein, the sulfoxide compound shown in the formula II is preferably any one of the following compounds;
wherein, the diazonium compound shown in the formula III is preferably ethyl diazoacetate and/or 2-benzyl diazoacetate.
Wherein, the S-diazoalkane compound shown in the formula I is preferably any one of the following compounds;
wherein the solvent of the first reaction liquid and the solvent of the second reaction liquid are respectively and independently selected from dichloromethane, acetone, 1, 2-dichloroethane, acetonitrile, N-dimethylformamide, N-dimethylacetamide and dimethyl sulfoxide or a plurality of combinations thereof, and preferably dichloromethane.
Wherein the molar concentration of the sulfoxide compound in the first reaction liquid is 0.2-2.5 mmol/mL.
Wherein the molar ratio of the sulfoxide compound to the diazonium compound is 1 (1-5), and preferably 1:1.2.
Wherein the molar ratio of the sulfoxide compound to the trifluoromethanesulfonic anhydride is 1 (1-5), and preferably 1:1.2.
Wherein the concentration of the trifluoromethanesulfonic anhydride in the second reaction solution is 0.04-3 mmol/mL.
The micro-channel reaction device comprises a feed pump (Baoding Leifu Fluid Technology Co.Ltd, (TYD 01-01-CE type)), a mixing module, a micro-channel 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 sequence, see fig. 1 and 2.
The micro-channel reactor is of a channel structure, the number of the channels is increased or reduced according to the requirement, the channel is made of polytetrafluoroethylene or Perfluoroalkoxyalkane (PFA), and the size and the inner diameter of the micro-channel reactor are 0.5-1.0 mm, preferably 0.6mm; the length is 5-20 m; the volume is 1 to 15.7mL, preferably 2.8mL.
Wherein the pumping rate ratio of the first reaction liquid to the second reaction liquid is 1 (0.5-1.5), and is preferably 1:1.
Wherein the pumping rates of the first reaction liquid and the second reaction liquid are 0.1-5.0 mL/min.
Wherein the reaction temperature is controlled to be-50 to 30 ℃, preferably-20 to 30 ℃, more preferably 20 to 30 ℃, and even more preferably room temperature.
Wherein the reaction time is 30s to 2.6 hours, preferably 5min to 60min, more preferably 5min to 30min, further preferably 5min to 10min, most preferably 7min.
The beneficial effects are that: compared with the prior art, the invention has the following advantages:
(1) The novel compound structure is obtained through synthesis, the reagent can be prepared by reacting sulfoxide compounds, diazonium compounds and trifluoromethanesulfonic anhydride through a microchannel reactor, and the reaction yield is high, the reaction condition is mild, the operation is simple, and the reagent has good amplifying synthesis potential.
(2) The invention can realize the synthesis of S-diazoalkane compounds at room temperature, avoids the harsh condition of ultralow temperature required by the original method, and reduces the synthesis cost.
(3) The method used by the invention can realize continuous synthesis and lay a foundation for amplification synthesis.
(4) The reactant related by the invention is accurately pumped by the injection pump, so that the dripping operation of the original method is avoided, the operation steps are simplified, and the safety of the process is improved.
(5) The product synthesized by the method does not need column chromatography separation, can be obtained through recrystallization operation, saves the solvent required by separation, and reduces the cost.
(6) The conversion rate of the product is 78-96%, and the yield is as high as 66-83%.
Drawings
FIG. 1 is a schematic illustration of the reaction scheme of the present invention.
FIG. 2 is a schematic diagram of a microchannel reactor.
FIG. 3 is a hydrogen spectrum of the product prepared in example 1.
FIG. 4 is a carbon spectrum of the product prepared in example 1.
FIG. 5 is a fluorine spectrum of the product prepared in example 1.
FIG. 6 is a hydrogen spectrum of the product prepared in example 5.
FIG. 7 is a carbon spectrum of the product prepared in example 5.
FIG. 8 is a fluorine spectrum of the product produced in example 5.
FIG. 9 is a hydrogen spectrum of the product prepared in example 6.
FIG. 10 is a carbon spectrum of the product prepared in example 6.
FIG. 11 is a fluorine spectrum of the product produced in example 6.
FIG. 12 is a hydrogen spectrum of the product prepared in example 7.
FIG. 13 is a carbon spectrum of the product prepared in example 7.
FIG. 14 is a fluorine spectrum of the product produced in example 7.
FIG. 15 is a hydrogen spectrum of the product prepared in example 8.
FIG. 16 is a carbon spectrum of the product prepared in example 8.
FIG. 17 is a fluorine spectrum of the product produced in example 8.
FIG. 18 is a hydrogen spectrum of the product prepared in example 9.
FIG. 19 is a carbon spectrum of the product prepared in example 9.
FIG. 20 is a fluorine spectrum of the product produced in example 9.
FIG. 21 is a hydrogen spectrum of the product prepared in example 10.
FIG. 22 is a graph of the carbon spectrum of the product prepared in example 10.
FIG. 23 is a fluorine spectrum of the product produced in example 10.
Detailed Description
The invention will be better understood from the following examples. However, it will be readily appreciated by those skilled in the art that the description of the embodiments is provided for illustration only and should not limit the invention as described in detail in the claims.
Example 1
2.02g (10.0 mmol,1.0 equiv) of diphenylsulfoxide was weighed out, 1.26mL (12.0 mmol,1.2 equiv) of ethyl diazoacetate was dissolved in methylene chloride, and a 10.0mL solution was prepared as a first reaction solution. 2.02mL of trifluoromethanesulfonic anhydride (12.0 mmol,1.2 equiv) was measured and dissolved in methylene chloride to prepare 10.0mL of a solution as a second reaction solution. The first reaction liquid and the second reaction liquid are respectively and simultaneously pumped into a micro-channel reactor (the inner diameter is 0.6mm, the volume is 2.8 mL), the pumping flow rates of the first reaction liquid and the second reaction liquid are respectively and simultaneously 0.2mL/min, and the reaction is carried out at the temperature of minus 50 ℃ and the residence time is 7.0min. After the reaction, TLC detection is carried out, the solvent is removed by reduced pressure distillation and recovered, and the methylene dichloride and the diethyl ether are recrystallized to obtain 2.96g of a final product, the yield is 66%, and the diphenyl sulfoxide conversion rate is 80%. As shown in fig. 3, 4, and 5, the characterization data are as follows: 1 H NMR(400MHz,Chloroform-d)δ7.95-7.84(m,4H),7.76(t,J＝7.4Hz,2H),7.72-7.65(m,4H),4.30(q,J＝7.1Hz,2H),1.27(t,J＝7.1Hz,3H). 13 CNMR(100MHz,Chloroform-d)δ159.1,134.7,131.3,130.6,124.0,120.7(q,J＝18.5Hz,1C),64.2,14.0. 19 F NMR(376MHz,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
2.02g (10.0 mmol,1.0 equiv) of diphenylsulfoxide was weighed out, 1.26mL (12.0 mmol,1.2 equiv) of ethyl diazoacetate was dissolved in methylene chloride, and a 10.0mL solution was prepared as a first reaction solution. 2.02mL of trifluoromethanesulfonic anhydride (12.0 mmol,1.2 equiv) was measured and dissolved in methylene chloride to prepare 10.0mL of a solution as a second reaction solution. The first reaction liquid and the second reaction liquid are respectively and simultaneously pumped into a micro-channel reactor (the inner diameter is 0.6mm, the volume is 2.8 mL), the pumping flow rates of the first reaction liquid and the second reaction liquid are respectively and simultaneously 0.2mL/min, and the reaction is carried out at the temperature of minus 20 ℃ and the residence time is 7.0min. After the reaction, TLC detection is carried out, the solvent is removed by distillation under reduced pressure and recovered, and the methylene dichloride and diethyl ether are recrystallized to obtain 3.04g of a final product, the yield is 68%, and the diphenyl sulfoxide conversion rate is 82%.
Example 3
2.02g (10.0 mmol,1.0 equiv) of diphenylsulfoxide was weighed out, 1.26mL (12.0 mmol,1.2 equiv) of ethyl diazoacetate was dissolved in methylene chloride, and a 10.0mL solution was prepared as a first reaction solution. 2.02mL of trifluoromethanesulfonic anhydride (12.0 mmol,1.2 equiv) was measured and dissolved in methylene chloride to prepare 10.0mL of a solution as a second reaction solution. The first reaction liquid and the second reaction liquid are respectively and simultaneously pumped into a micro-channel reactor (the inner diameter is 0.6mm, the volume is 2.8 mL), the pumping flow rates of the first reaction liquid and the second reaction liquid are respectively and simultaneously 0.2mL/min, the reaction is carried out at the temperature of 0 ℃ and the residence time is 7.0min. After the reaction, TLC detection is carried out, the solvent is removed by distillation under reduced pressure and recovered, and the methylene dichloride and the diethyl ether are recrystallized to obtain 3.36g of a final product, the yield is 75%, and the conversion rate of diphenyl sulfoxide is 88%.
Example 4
2.02g (10.0 mmol,1.0 equiv) of diphenylsulfoxide was weighed out, 1.26mL (12.0 mmol,1.2 equiv) of ethyl diazoacetate was dissolved in methylene chloride, and a 10.0mL solution was prepared as a first reaction solution. 2.02mL of trifluoromethanesulfonic anhydride (12.0 mmol,1.2 equiv) was measured and dissolved in methylene chloride to prepare 10.0mL of a solution as a second reaction solution. The first reaction liquid and the second reaction liquid are respectively and simultaneously pumped into a micro-channel reactor (the inner diameter is 0.6mm, the volume is 2.8 mL), the pumping flow rates of the first reaction liquid and the second reaction liquid are respectively and simultaneously 0.2mL/min, the reaction is carried out at room temperature, and the residence time is 7.0min. After the reaction, TLC detection was performed, the solvent was distilled off under reduced pressure and recovered, and methylene chloride and diethyl ether were recrystallized to obtain 3.71g of a final product, yield 83%, and diphenyl sulfoxide conversion 95%.
Example 5
Weighing 4,4' -dichloro diphenyl0.54g (2.0 mmol,1.0 equiv) of methyl sulfoxide and 0.25mL (2.4 mmol,1.2 equiv) of ethyl diazoacetate were dissolved in methylene chloride to prepare 10.0mL of a solution as a first reaction solution. 0.40mL of trifluoromethanesulfonic anhydride (2.4 mmol,1.2 equiv) was measured and dissolved in methylene chloride to prepare 10.0mL of a solution as a second reaction solution. The first reaction liquid and the second reaction liquid are respectively and simultaneously pumped into a micro-channel reactor (the inner diameter is 0.6mm, the volume is 2.8 mL), the pumping flow rates of the first reaction liquid and the second reaction liquid are respectively and simultaneously 0.2mL/min, the reaction is carried out at room temperature, and the residence time is 7.0min. After the reaction, TLC detection is carried out, the solvent is removed by distillation under reduced pressure and recovered, and methylene dichloride and diethyl ether are recrystallized to obtain 0.78g of final product, the yield is 76%, and the conversion rate of 4,4' -dichloro diphenyl sulfoxide is 88%. As shown in fig. 6, 7, and 8, the characterization data are as follows: 1 H NMR(400MHz,DMSO-d 6 )δ7.98(d,J＝8.8Hz,4H),7.85(d,J＝8.8Hz,4H),4.20(q,J＝7.0Hz,2H),1.13(t,J＝7.0Hz,3H). 13 C NMR(100MHz,DMSO-d 6 )δ159.7,139.6,133.0,131.0,124.5,63.9,59.5,14.3. 19 F NMR(376MHz,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
1.15g (5.0 mmol,1.0 equiv) of 4,4' -xylyl sulfoxide was weighed out, and 0.63mL (6.0 mmol,1.2 equiv) of ethyl diazoacetate was dissolved in methylene chloride to prepare 10.0mL of a solution as a first reaction solution. 1.0mL of trifluoromethanesulfonic anhydride (6.0 mmol,1.2 equiv) was measured and dissolved in methylene chloride to prepare 10.0mL of a solution as a second reaction solution. The first reaction liquid and the second reaction liquid are respectively and simultaneously pumped into a micro-channel reactor (the inner diameter is 0.6mm, the volume is 2.8 mL), the pumping flow rates of the first reaction liquid and the second reaction liquid are respectively and simultaneously 0.2mL/min, the reaction is carried out at room temperature, and the residence time is 7.0min. TLC detection is carried out after the reaction is finished, the solvent is removed by reduced pressure distillation and recovered, and the methylene dichloride and the diethyl ether are recrystallized to obtain the final product1.86g of product was obtained in 78% yield with 89% conversion of 4,4' -dimethylbenzene sulfoxide. As shown in fig. 9, 10, and 11, the characterization data are as follows: 1H NMR (400 MHz, DMSO-d 6) delta 7.81 (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-d 6) delta 159.9,145.4,131.7,130.9,121.9,63.8,60.2,21.4,14.3.19F NMR (376 MHz, chloroform-d) delta 77.78.HRMS (ESI) m/z: calcd for C 18 H 19 N 2 O 2 S + [M-OTf] + :327.1162,found:327.1152.
Example 7
1.16g (5.0 mmol,1.0 equiv) of thianthrene 5-oxide, 0.63mL (6.0 mmol,1.2 equiv) of ethyl diazoacetate was weighed out, dissolved in methylene chloride, and 20.0mL of the solution was prepared as a first reaction solution. 1.0mL of trifluoromethanesulfonic anhydride (6.0 mmol,1.2 equiv) was measured and dissolved in methylene chloride to prepare 20.0mL of a solution as a second reaction solution. The first reaction liquid and the second reaction liquid are respectively and simultaneously pumped into a micro-channel reactor (the inner diameter is 0.6mm, the volume is 2.8 mL), the pumping flow rates of the first reaction liquid and the second reaction liquid are respectively and simultaneously 0.2mL/min, the reaction is carried out at room temperature, and the residence time is 7.0min. After the reaction, TLC detection is carried out, the solvent is removed by reduced pressure distillation and recovered, and methylene dichloride and diethyl ether are recrystallized to obtain 1.96g of final product, the yield is 82%, and the conversion rate of thianthrene 5-oxide is 95%. As shown in fig. 12, 13, and 14, the characterization data are as follows: 1 H NMR(400MHz,Chloroform-d)δ8.43(d,J＝7.7Hz,2H),7.91(d,J＝7.7Hz,2H),7.82(t,J＝7.5Hz,2H),7.72(t,J＝7.6Hz,2H),4.30(q,J＝7.1Hz,2H),1.28(t,J＝7.1Hz,3H). 13 C NMR(100MHz,Chloroform-d)δ159.6,136.3,135.2,134.6,130.4,130.3,120.8(q,J＝318.7Hz,1C),117.1,64.3,61.4,14.1. 19 F NMR(376MHz,Chloroform-d)δ77.19.HRMS(ESI)m/z:calcd for C 16 H 13 ClN 2 O 2 S 2 + [M-OTf] + :329.0413,found:329.0406.
example 8
0.61g (2.0 mmol,1.0 equiv) of 2,3,7, 8-tetrafluorothianthrene 5-oxide was weighed out, and 0.25mL (2.4 mmol,1.2 equiv) of ethyl diazoacetate was dissolved in methylene chloride to prepare 10.0mL of a solution as a first reaction solution. 0.40mL of trifluoromethanesulfonic anhydride (2.4 mmol,1.2 equiv) was measured and dissolved in methylene chloride to prepare 10.0mL of a solution as a second reaction solution. The first reaction liquid and the second reaction liquid are respectively and simultaneously pumped into a micro-channel reactor (the inner diameter is 0.6mm, the volume is 2.8 mL), the pumping flow rates of the first reaction liquid and the second reaction liquid are respectively and simultaneously 0.2mL/min, the reaction is carried out at room temperature, and the residence time is 7.0min. After the reaction, TLC detection was performed, the solvent was distilled off under reduced pressure and recovered, and methylene chloride and diethyl ether were recrystallized to give 0.91g of the final product, yield 83%, and conversion of 2,3,7, 8-tetrafluorothianthrene 5-oxide was 93%. As shown in fig. 15, 16, and 17, the characterization data are as follows: 1 H NMR(400MHz,DMSO-d 6 )δ8.73–8.52(m,2H),8.40–8.23(m,2H),4.21(q,J＝7.0Hz,2H),1.16(t,J＝7.0Hz,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
0.4g (2.0 mmol,1.0 equiv) of dibenzothiophene 5-oxide was weighed out, and 0.25mL (2.4 mmol,1.2 equiv) of ethyl diazoacetate was dissolved in methylene chloride to prepare 10.0mL of a solution as a first reaction solution. 0.4mL of trifluoromethanesulfonic anhydride (2.4 mmol,1.2 equiv) was measured and dissolved in methylene chloride to prepare 10.0mL of a solution as a second reaction solution. First reaction liquidThe second reaction liquid is respectively and simultaneously pumped into the micro-channel reactor (the inner diameter is 0.6mm, the volume is 2.8 mL), the pumping flow rates of the first reaction liquid and the second reaction liquid are respectively and simultaneously 0.2mL/min, the reaction is carried out at room temperature, and the residence time is 7.0min. After the reaction, TLC detection was performed, the solvent was distilled off under reduced pressure and recovered, and methylene chloride and diethyl ether were recrystallized to obtain 0.77g of a final product, yield 83%, and dibenzothiophene 5-oxide conversion 96%. As shown in fig. 18, 19, and 20, the characterization data are as follows: 1 H NMR(400MHz,DMSO-d 6 )δ8.52(d,J＝7.9Hz,2H),8.39(d,J＝7.4Hz,2H),7.94–7.85(m,2H),7.79–7.71(m,2H),3.78(q,J＝7.0Hz,2H),0.74(t,J＝6.7Hz,3H). 13 C NMR(100MHz,DMSO-d 6 )δ158.9,139.8,134.2,131.3,131.2,128.3,124.1,121.2(q,J＝20.4Hz,1C),63.2,60.6,13.8. 19 F NMR(376MHz,Chloroform-d)δ77.74.HRMS(ESI)m/z:calcd for C 16 H 13 N 2 O 2 S + [M-OTf] + :297.0692,found:297.0688.
example 10
0.4g (2.0 mmol,1.0 equiv) of dibenzothiophene 5-oxide, 0.42g (2.4 mmol,1.2 equiv) of benzyl 2-diazoacetate, and 10.0mL of the solution was prepared as a first reaction solution by dissolving the dibenzothiophene 5-oxide in methylene chloride. 0.4mL of trifluoromethanesulfonic anhydride (2.4 mmol,1.2 equiv) was measured and dissolved in methylene chloride to prepare 10.0mL of a solution as a second reaction solution. The first reaction liquid and the second reaction liquid are respectively and simultaneously pumped into a micro-channel reactor (the inner diameter is 0.6mm, the volume is 2.8 mL), the pumping flow rates of the first reaction liquid and the second reaction liquid are respectively and simultaneously 0.2mL/min, the reaction is carried out at room temperature, and the residence time is 7.0min. After the reaction, TLC detection is carried out, the solvent is removed by distillation under reduced pressure and recovered, and methylene dichloride and diethyl ether are recrystallized to obtain 0.81g of final product, the yield is 80%, and the conversion rate of dibenzothiophene 5-oxide is 92%. As shown in fig. 21, 22, and 23, the characterization data are as follows: 1 H NMR(400MHz,DMSO-d 6 )δ8.50(d,J＝7.8Hz,2H),8.22(d,J＝7.2Hz,2H),7.84(t,J＝7.3Hz,2H),7.73(t,J＝7.5Hz,2H),7.38–7.15(m,3H),6.87(s,2H),4.80(s,2H). 13 C NMR(100MHz,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)δ77.73.
comparative example 1
2.02g (10.0 mmol,1.0 equiv) of diphenylsulfoxide was weighed, dissolved in 20.0mL of methylene chloride, and 1.26mL (12.0 mmol,1.2 equiv) of ethyl diazoacetate was added thereto, 2.02mL of trifluoromethanesulfonic anhydride was measured, and the mixture was slowly added dropwise. The reaction was stirred at room temperature for 6h, after the completion of the reaction, TLC was performed, the solvent was distilled off under reduced pressure and recovered, and methylene chloride and diethyl ether were recrystallized to give 2.96g of the final product in 66% yield and 80% conversion of diphenyl sulfoxide.
Comparative examples 2 to 6
Referring to comparative example 1, the reactions were carried out under the same conditions based on the substrates in examples 5 to 10 alone, and the yields of the respective comparative examples are shown in Table 1.
TABLE 1
[a] Reaction conditions: and respectively weighing a substrate I and a substrate II, dissolving in dichloromethane to obtain a reaction solution I, dissolving the trifluoromethanesulfonic anhydride in dichloromethane to obtain a reaction solution II, simultaneously pumping the reaction solution II into a microchannel reactor to perform reaction, distilling under reduced pressure to remove a solvent after the reaction is finished, and recrystallizing the dichloromethane and diethyl ether to obtain a product.
[b] Reaction conditions: and (3) respectively weighing a substrate I and a substrate II, dissolving in dichloromethane, slowly dropwise adding trifluoromethanesulfonic anhydride into the reaction solution, stirring at room temperature for reaction for 6 hours, removing a solvent by reduced pressure distillation after the reaction is finished, and recrystallizing the dichloromethane and diethyl ether to obtain a product.
The invention provides a thought and a method for preparing an S-alkynyl functional reagent by utilizing a microchannel reactor, and the method and the way for realizing the technical scheme are numerous, the above is only a preferred embodiment of the invention, and it should be pointed out that a plurality of improvements and modifications can be made by those skilled in the art without departing from the principle of the invention, and the improvements and the modifications are also considered as the protection scope of the invention. The components not explicitly described in this embodiment can be implemented by using the prior art.
Claims (10)
1. A method for preparing S-diazoalkane compounds by utilizing a micro-channel reaction device is characterized in that a first reaction liquid containing sulfoxide compounds and diazo compounds reacts with a second reaction liquid containing trifluoromethanesulfonic anhydride in the micro-channel reaction device to obtain a reaction liquid containing S-diazoalkane compounds;
the sulfoxide compound is any one of the following compounds;
the diazonium compound is ethyl diazoacetate and/or 2-benzyl 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 each independently selected from dichloromethane, acetone, 1, 2-dichloroethane, acetonitrile, N-dimethylformamide, N-dimethylacetamide, dimethylsulfoxide, or a combination thereof.
3. The method according to claim 1, wherein the concentration of the sulfoxide compound in the first reaction liquid is 0.2 to 2.5mmol/mL.
4. The method according to claim 1, wherein the molar ratio of sulfoxide compound to diazonium compound is 1 (1-5).
5. The method according to claim 1, wherein the molar ratio of sulfoxide compound to trifluoromethanesulfonic anhydride is 1 (1-5).
6. The method according to claim 1, wherein the concentration of trifluoromethanesulfonic anhydride in the second reaction solution is 0.04 to 3mmol/mL.
7. The method according to claim 1, wherein the inner diameter of the microchannel reactor in the microchannel reactor is 0.5-1.0 mm.
8. The method according to claim 1, wherein the length of the microchannel reactor in the microchannel reactor is 5-20 m.
9. The method of claim 1, wherein the ratio of the pumping rates of the first reaction solution to the second reaction solution is 1 (0.5 to 1.5).
10. The method according to claim 1, wherein the temperature of the reaction is-50 to 30 ℃.
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