CN103896737A - Method for preparing propargyl alcohol by utilizing microstructure reactor - Google Patents
Method for preparing propargyl alcohol by utilizing microstructure reactor Download PDFInfo
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- 238000000034 method Methods 0.000 title claims abstract description 40
- TVDSBUOJIPERQY-UHFFFAOYSA-N prop-2-yn-1-ol Chemical compound OCC#C TVDSBUOJIPERQY-UHFFFAOYSA-N 0.000 title claims abstract description 23
- 238000006243 chemical reaction Methods 0.000 claims abstract description 136
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims abstract description 56
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims abstract description 56
- -1 acetenyl magnesium bromide Grignard reagent Chemical class 0.000 claims abstract description 38
- 239000007818 Grignard reagent Substances 0.000 claims abstract description 32
- 150000004795 grignard reagents Chemical class 0.000 claims abstract description 30
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 10
- 238000006460 hydrolysis reaction Methods 0.000 claims abstract description 9
- 238000005935 nucleophilic addition reaction Methods 0.000 claims abstract description 9
- FRIJBUGBVQZNTB-UHFFFAOYSA-M magnesium;ethane;bromide Chemical compound [Mg+2].[Br-].[CH2-]C FRIJBUGBVQZNTB-UHFFFAOYSA-M 0.000 claims description 33
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims description 30
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 22
- 230000031709 bromination Effects 0.000 claims description 22
- 238000005893 bromination reaction Methods 0.000 claims description 22
- 239000011777 magnesium Substances 0.000 claims description 22
- 229910052749 magnesium Inorganic materials 0.000 claims description 22
- 235000019270 ammonium chloride Nutrition 0.000 claims description 15
- 150000002576 ketones Chemical class 0.000 claims description 10
- 125000003118 aryl group Chemical group 0.000 claims description 8
- 150000001299 aldehydes Chemical class 0.000 claims description 7
- 230000000887 hydrating effect Effects 0.000 claims description 6
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical group [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 claims description 5
- 230000035484 reaction time Effects 0.000 claims description 5
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 125000004799 bromophenyl group Chemical group 0.000 claims description 4
- 125000001207 fluorophenyl group Chemical group 0.000 claims description 4
- 125000005504 styryl group Chemical group 0.000 claims description 4
- 125000001680 trimethoxyphenyl group Chemical group 0.000 claims description 4
- PAWQVTBBRAZDMG-UHFFFAOYSA-N 2-(3-bromo-2-fluorophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC(Br)=C1F PAWQVTBBRAZDMG-UHFFFAOYSA-N 0.000 claims description 3
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 3
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 claims description 3
- 229910052921 ammonium sulfate Inorganic materials 0.000 claims description 3
- 235000011130 ammonium sulphate Nutrition 0.000 claims description 3
- 238000000746 purification Methods 0.000 claims description 2
- 238000000926 separation method Methods 0.000 claims description 2
- 238000010189 synthetic method Methods 0.000 claims description 2
- 239000002994 raw material Substances 0.000 abstract description 15
- 230000007062 hydrolysis Effects 0.000 abstract 1
- 238000009776 industrial production Methods 0.000 abstract 1
- 239000007791 liquid phase Substances 0.000 abstract 1
- 238000007670 refining Methods 0.000 abstract 1
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 62
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 31
- 239000000243 solution Substances 0.000 description 25
- 238000005481 NMR spectroscopy Methods 0.000 description 20
- 239000011259 mixed solution Substances 0.000 description 17
- 239000000203 mixture Substances 0.000 description 16
- 230000009466 transformation Effects 0.000 description 16
- 239000007788 liquid Substances 0.000 description 12
- 238000003818 flash chromatography Methods 0.000 description 8
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- AUHZEENZYGFFBQ-UHFFFAOYSA-N 1,3,5-trimethylbenzene Chemical compound CC1=CC(C)=CC(C)=C1 AUHZEENZYGFFBQ-UHFFFAOYSA-N 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- OPHQOIGEOHXOGX-UHFFFAOYSA-N 3,4,5-trimethoxybenzaldehyde Chemical compound COC1=CC(C=O)=CC(OC)=C1OC OPHQOIGEOHXOGX-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- KJPRLNWUNMBNBZ-QPJJXVBHSA-N (E)-cinnamaldehyde Chemical compound O=C\C=C\C1=CC=CC=C1 KJPRLNWUNMBNBZ-QPJJXVBHSA-N 0.000 description 1
- QYLFHLNFIHBCPR-UHFFFAOYSA-N 1-ethynylcyclohexan-1-ol Chemical compound C#CC1(O)CCCCC1 QYLFHLNFIHBCPR-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- ZRYZBQLXDKPBDU-UHFFFAOYSA-N 4-bromobenzaldehyde Chemical compound BrC1=CC=C(C=O)C=C1 ZRYZBQLXDKPBDU-UHFFFAOYSA-N 0.000 description 1
- AVPYQKSLYISFPO-UHFFFAOYSA-N 4-chlorobenzaldehyde Chemical compound ClC1=CC=C(C=O)C=C1 AVPYQKSLYISFPO-UHFFFAOYSA-N 0.000 description 1
- UOQXIWFBQSVDPP-UHFFFAOYSA-N 4-fluorobenzaldehyde Chemical compound FC1=CC=C(C=O)C=C1 UOQXIWFBQSVDPP-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 235000014493 Crataegus Nutrition 0.000 description 1
- 241001092040 Crataegus Species 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000001345 alkine derivatives Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 239000001166 ammonium sulphate Substances 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000006757 chemical reactions by type Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 238000005260 corrosion Methods 0.000 description 1
- 230000007797 corrosion Effects 0.000 description 1
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- YLQWCDOCJODRMT-UHFFFAOYSA-N fluoren-9-one Chemical compound C1=CC=C2C(=O)C3=CC=CC=C3C2=C1 YLQWCDOCJODRMT-UHFFFAOYSA-N 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- AFRJJFRNGGLMDW-UHFFFAOYSA-N lithium amide Chemical compound [Li+].[NH2-] AFRJJFRNGGLMDW-UHFFFAOYSA-N 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- ZRSNZINYAWTAHE-UHFFFAOYSA-N p-methoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C=C1 ZRSNZINYAWTAHE-UHFFFAOYSA-N 0.000 description 1
- HGBOYTHUEUWSSQ-UHFFFAOYSA-N pentanal Chemical compound CCCCC=O HGBOYTHUEUWSSQ-UHFFFAOYSA-N 0.000 description 1
- 238000007747 plating Methods 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000011949 solid catalyst Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229920002994 synthetic fiber Polymers 0.000 description 1
- DQFBYFPFKXHELB-VAWYXSNFSA-N trans-chalcone Chemical compound C=1C=CC=CC=1C(=O)\C=C\C1=CC=CC=C1 DQFBYFPFKXHELB-VAWYXSNFSA-N 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/36—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring increasing the number of carbon atoms by reactions with formation of hydroxy groups, which may occur via intermediates being derivatives of hydroxy, e.g. O-metal
- C07C29/38—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring increasing the number of carbon atoms by reactions with formation of hydroxy groups, which may occur via intermediates being derivatives of hydroxy, e.g. O-metal by reaction with aldehydes or ketones
- C07C29/42—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring increasing the number of carbon atoms by reactions with formation of hydroxy groups, which may occur via intermediates being derivatives of hydroxy, e.g. O-metal by reaction with aldehydes or ketones with compounds containing triple carbon-to-carbon bonds, e.g. with metal-alkynes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/01—Preparation of ethers
- C07C41/18—Preparation of ethers by reactions not forming ether-oxygen bonds
- C07C41/30—Preparation of ethers by reactions not forming ether-oxygen bonds by increasing the number of carbon atoms, e.g. by oligomerisation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2603/00—Systems containing at least three condensed rings
- C07C2603/02—Ortho- or ortho- and peri-condensed systems
- C07C2603/04—Ortho- or ortho- and peri-condensed systems containing three rings
- C07C2603/06—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members
- C07C2603/10—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings
- C07C2603/12—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings only one five-membered ring
- C07C2603/18—Fluorenes; Hydrogenated fluorenes
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention provides a method for preparing propargyl alcohol by utilizing a microstructure reactor, which is characterized in that a simple Grignard reagent is used as a raw material to generate a Grignard exchange reaction of a gas-liquid phase with acetylene gas in the microstructure reactor to generate a high-quality acetenyl magnesium bromide Grignard reagent; and carrying out nucleophilic addition reaction on the obtained ethynyl magnesium bromide Grignard reagent and electrophilic reagent in another microstructure reactor under the condition of continuous flow, and separating and refining the product after hydrolysis to obtain the substituted propargyl alcohol product. The method has the advantages of simple operation, simple, cheap and easily obtained raw materials and reagents, continuous, rapid and controllable process, mild condition, good product selectivity and realization of industrial production.
Description
Technical field
The present invention relates to a kind of method of preparing propargyl alcohol, relate in particular to a kind of method of utilizing micro-structured reactor to prepare propargyl alcohol.
Background technology
The replacement propargyl alcohol with following formula structure is the important synthetic intermediate of a class, is mainly used in the field such as medicine, synthetic materials, also can be used as the lustering agent of nickel plating or copper etc.Under high temperature, high pressure, concentrated acid condition, propargyl alcohol has the good ability that prevents metallic corrosion.
The synthetic method of Chinese patent CN102701911A mainly contains dry acetylene gas, pass into Grignard reagent or lithium reagent under low temperature (78 ℃) in, carry out Ge Shi exchange, or under liquefied ammonia environment, pass in sodium amide or Lithamide, or pass in the tetrahydrofuran solution of potassium tert.-butoxide, then ketone or aldehyde splashing in above-mentioned reaction solution slowly obtained to alkynol.Chinese patent CN102476978A, CN1769254A reacts and prepares alkynol based on Favorski, i.e. and alkynol is prepared in ketone and alkynes reaction under alkalescence (solid potassium hydroxide) catalyst action.At normal pressure and suitable temperature, acetylene is passed in the organic solvent (solid catalyst potassium hydroxide is with in the Powdered mixed solution that is suspended in organic solvent and ketone) that is dissolved with ketone and reacted.A kind of method that U.S. Pat 6147266, Chinese patent CN1247849A propose fixed bed and produce continuously alkynol, employing anionite-exchange resin is catalyzer, this process low conversion rate.Whole reaction process is difficult to realize operate continuously, condition harshness, and process is loaded down with trivial details, higher to operation and equipment requirements, is not suitable for suitability for industrialized production.
Micro-reaction technology has enhancement of heat transfer, mass transfer, easy handling, safe and reliable and without advantages such as scale effects; show wide application prospect at aspects such as the energy, chemical industry, organic synthesis and fine chemicals; especially aspect strong exothermal reaction type, also there are being many application (Chambers, R.D.; Spink, R.C.H.Chem.Commun.1999,10,883.; Wada, Y.; Schmidt, M.A.; Jensen, K.F.Ind.Eng.Chem.Res.2006,45,8036.).In micro-structured reactor, prepare Grignard reagent document and have been reported (Wakami H.; Yoshida J.Org.Process.Res.Dev.2005,9,787.), also do not have report but use gas to carry out Ge Shi exchange system as raw material with simple Ge Shi for the method for propargyl alcohol.
Summary of the invention
The object of this invention is to provide a kind of simple and direct, the micro-structured reactor that utilizes efficient, highly selective is prepared the method for propargyl alcohol rapidly, continuously.
Technical scheme of the present invention is: a kind of method of utilizing micro-structured reactor to prepare propargyl alcohol, and its concrete steps are as follows:
(1) Ge Shi exchange: in micro-structured reactor, Ge Shi permutoid reaction occurs for acetylene gas and Grignard reagent;
(2) nucleophilic addition(Adn): in micro-structured reactor, by step (1) product and electrophilic reagent generation nucleophilic addition;
(3) hydrolysis reaction: in micro-structured reactor, step (2) product, through hydrating solution generation hydrolysis reaction, is obtained replacing the thick product of propargyl alcohol;
(4) replace the thick product of propargyl alcohol through separation, purification, obtain replacing propargyl alcohol.
Preferably above-mentioned Grignard reagent is methyl-magnesium-bromide, ethylmagnesium bromide, normal-butyl bromination magnesium or allyl group bromination magnesium; More preferably Grignard reagent is ethylmagnesium bromide or methyl-magnesium-bromide.
Preferably above-mentioned electrophilic reagent is aldehydes or ketones solution, and the structural formula of aldehydes or ketones is as R
1c (O) R
2, wherein R
1for alkyl C
nh
2n+1(n=1~5) or aromatic base, aromatic base is p-methoxy-phenyl, bromophenyl, chloro-phenyl-, fluorophenyl, trimethoxyphenyl or styryl; R2 alkyl C
nh
2n+1(n=1~5) or aromatic base, aromatic base is p-methoxy-phenyl, bromophenyl, chloro-phenyl-, fluorophenyl, trimethoxyphenyl or styryl.Solvent in electrophilic reagent is preferably tetrahydrofuran (THF), normal hexane or ether.Preferably the concentration of aldehydes or ketones solution is 0.01~5mol/L.
Preferably above-mentioned hydrating solution is proton type solvent, more preferably ammonium chloride, dilute hydrochloric acid, ammonium sulfate or ammonium nitrate.For can there is hydrolysis reaction in the amount of hydrating solution.
Preferably the micro-structured reactor in above-mentioned steps (1), (2) and (3) includes micro mixer and micro passage reaction, and micro mixer and micro passage reaction link together.Preferably above-mentioned micro passage reaction passage internal diameter (diameter) is 0.1~10mm; Micro mixer internal diameter (diameter) is of a size of 0.021~10mm.Be characterized in that internal flow contact area is large, conduct heat, mass transfer velocity is fast, process can realize operate continuously.Can realize number and increase amplification, produce as required, without scale effect.
Temperature of reaction in preferred steps (1) is-20~30 ℃; Be preferably-5~0 ℃; Temperature of reaction in step (2) is 20~40 ℃; Temperature of reaction in step (3) is 20~40 ℃.
Preferably the Ge Shi permutoid reaction time is 5s~30min; The nucleophilic addition residence time is 6s~50min; The hydrolysis reaction residence time is 10s~10min.
In the method for synthetic replacement propargyl alcohol of the present invention, in Ge Shi permutoid reaction, acetylene gas flow velocity and Grignard reagent velocity ratio are 4~300, the Ge Shi permutoid reaction time is that 5s~30min(does not calculate the reaction times at micro mixer, the reaction times of micro mixer ignores), the nucleophilic addition residence time is 6s~50min, and the mol ratio of Grignard reagent and electrophilic reagent is 1:1.2~1:0.5; The hydrolysis reaction residence time is 10s~10min.
The selectivity of the replacement propargyl alcohol that the present invention synthesizes is all greater than 91%, yield 87~96%.
Beneficial effect:
The present invention has overcome the drawback of traditional method, has the following advantages: 1) reaction conditions gentleness; 2) product has the selectivity of height; 3) simple to operate, can realize continuous, controllable operating; 4), according to Production requirement, can realize the production of mass-producing and without scale effect.
Innovative point of the present invention is to provide a kind of multiple micro-structured reactor series connection to use, and realized mild condition, the process method of the synthetic replacement propargyl alcohol of controlled, highly selective continuously.Mass transfer, heat-transfer capability that the present invention utilizes micro-structured reactor to have advantages of are strong, the ultra-low temperature surroundings requirement of having avoided traditional Ge Shi clearing house to need, and realized continuous operation.
Accompanying drawing explanation
It in figure, is the synthetic device schematic flow sheet that replaces propargyl alcohol of micro-structured reactor; A1, A2, A3 are high pressure syringe pump, A4 is ram pump, B1, B2, B3 are micro mixer, and C1, C2, C3 are micro passage reaction, and D1, D2 are thermostat container, E is product-collecting bottle, F is mass flow controller, and R1 is Grignard reagent, and R2 is acetylene, R3 aldehyde solution or ketone solution, R4 is hydrating solution.
Embodiment
Following examples contribute to understand the present invention, but are not limited to summary of the invention.In this area, the simple replacement that technician does the present invention or improve and all belong to the technical scheme that the present invention protects within.
Embodiment 1
As shown in Figure 1: ethylmagnesium bromide is injected micro mixer B1(intersection toe type micro mixer by high pressure syringe pump A1, HPIMM, IMM, Germany, length×width×height=25 × 21 × 37 μ m) be metered into acetylene gas by F and react, ethylmagnesium bromide is than acetylene gas velocity ratio 1:300, at thermostat container D1(0 ℃) in there is Ge Shi permutoid reaction, enter micro passage reaction C1(internal diameter: 1mm) continuation reaction 10s, product ethynyl bromination magnesium pumps into micro mixer B2(V2 by ram pump A4, IMM, Germany) with the tetrahydrofuran (THF) mixed solution (0.1mol/L) that is pumped into phenyl aldehyde by high pressure syringe pump A2 at thermostat container D2(25 ℃) in mix, the mol ratio of Grignard reagent and phenyl aldehyde is 1:1, then enter micro passage reaction C2(internal diameter: 1mm) continuation reaction 20s, the product obtaining enters the threeway of micro mixer B3(T-type, internal diameter: 1mm) with pump into ammonium chloride solution at thermostat container D2(25 ℃ by syringe pump A3) in react, then enter micro passage reaction C3(internal diameter: 1mm) continue reaction 2min enter product-collecting bottle E.Product G C analyzes transformation efficiency 56%, 1-phenyl-2-propargyl alcohol selectivity 59%.The test data of embodiment 1~16 is:
1h NMR (400MHz, CDCl
3): δ 7.55-7.53 (d, 2H, J=7.2Hz), 7.40-7.32 (m, 3H), 5.40 (d, 1H, J=1.2Hz), 2.65 (d, 1H, J=2Hz), 2.55 (s, 1H).
13c NMR (400MHz, CDCl
3): δ 140.0,128.7,128.5,126.6,83.5,74.8,64.4.
Embodiment 2
As shown in Figure 1: ethylmagnesium bromide is injected micro mixer B1(Caterpillar by high pressure syringe pump A1, IMM, Germany, length x width=300 × 300 μ m) be metered into acetylene gas by F and react, ethylmagnesium bromide is than acetylene gas velocity ratio 1:100, at thermostat container D1(0 ℃) in there is Ge Shi permutoid reaction, enter micro passage reaction C1(internal diameter: 0.5mm) continuation reaction 5s, product ethynyl bromination magnesium pumps into micro mixer B2(intersection toe type micro mixer by ram pump A4, HPIMM, IMM, Germany, length×width×height=25 × 21 × 37 μ m) with the tetrahydrofuran (THF) mixed solution (1mol/L) that is pumped into phenyl aldehyde by high pressure syringe pump A2 at thermostat container D2(25 ℃) in mix, the mol ratio of Grignard reagent and phenyl aldehyde is 1:1.2, then enter micro passage reaction C2(internal diameter: 1mm) continuation reaction 6s, the product obtaining enters the threeway of micro mixer B3(T-type, internal diameter: 1mm) with pump into ammoniumsulphate soln at thermostat container D2(25 ℃ by syringe pump A3) in react, then enter micro passage reaction C3(internal diameter: 5mm) continue reaction 10min enter product-collecting bottle E.Product G C analyzes transformation efficiency 45%, 1-phenyl-2-propargyl alcohol selectivity 77%.
Embodiment 3
As shown in the figure: ethylmagnesium bromide is injected falling liquid film micro-structured reactor B1(length x width by high pressure syringe pump A1: 300 × 100 μ m) be metered into acetylene gas by F and react, ethylmagnesium bromide is than acetylene gas velocity ratio 1:50, at thermostat container D1(0 ℃) in there is Ge Shi permutoid reaction, enter micro passage reaction C1(internal diameter: 3mm) continuation reaction 2min, product ethynyl bromination magnesium pumps into the threeway of micro mixer B2(T-type by ram pump A4, internal diameter: 1mm) with the tetrahydrofuran (THF) mixed solution (3mol/L) that is pumped into phenyl aldehyde by high pressure syringe pump A2 at thermostat container D2(25 ℃) in mix, the mol ratio of Grignard reagent and phenyl aldehyde is 1:0.8, then enter micro passage reaction C2(internal diameter: 1mm) continuation reaction 2min, the product obtaining enters the threeway of micro mixer B3(T-type, internal diameter: 6mm) with pump into dilute hydrochloric acid solution at thermostat container D2(25 ℃ by syringe pump A3) in react, then enter micro passage reaction C3(internal diameter: 10mm) continue reaction 8min enter product-collecting bottle E.Product G C analyzes transformation efficiency 46%, 1-phenyl-2-propargyl alcohol selectivity 95%.
Embodiment 4
As shown in the figure: ethylmagnesium bromide is injected falling liquid film micro-structured reactor B1(length x width by high pressure syringe pump A1: 300 × 100 μ m) be metered into acetylene gas by F and react, ethylmagnesium bromide is than acetylene gas velocity ratio 1:25, at thermostat container D1(0 ℃) in there is Ge Shi permutoid reaction, enter micro passage reaction C1(internal diameter: 1mm) continuation reaction 5min, product ethynyl bromination magnesium pumps into micro mixer B2(Caterpillar by ram pump A4, IMM, Germany, length x width: 300 × 300 μ m) with the tetrahydrofuran (THF) mixed solution (5mol/L) that is pumped into phenyl aldehyde by high pressure syringe pump A2 at thermostat container D2(25 ℃) in mix, the mol ratio of Grignard reagent and phenyl aldehyde is 1:1, then enter micro passage reaction C2(internal diameter: 1mm) continuation reaction 5min, the product obtaining enters the threeway of micro mixer B3(T-type, internal diameter: 1mm) with pump into ammonium nitrate solution at thermostat container D2(25 ℃ by syringe pump A3) in react, then enter micro passage reaction C3(internal diameter: 10mm) continue reaction 10min enter product-collecting bottle E.Product G C analyzes transformation efficiency 50%, 1-phenyl-2-propargyl alcohol selectivity 93%.
Embodiment 5
As shown in the figure: ethylmagnesium bromide is injected falling liquid film micro-structured reactor B1(length x width by high pressure syringe pump A1: 300 × 100 μ m) be metered into acetylene gas by F and react, ethylmagnesium bromide is than acetylene gas velocity ratio 1:10, at thermostat container D1(0 ℃) in there is Ge Shi permutoid reaction, enter micro passage reaction C1(internal diameter: 5mm) continuation reaction 10min, product ethynyl bromination magnesium pumps into the threeway of micro mixer B2(T-type by ram pump A4, internal diameter: 1mm) with the tetrahydrofuran (THF) mixed solution (0.5mol/L) that is pumped into phenyl aldehyde by high pressure syringe pump A2 at thermostat container D2(25 ℃) in mix, the mol ratio of Grignard reagent and phenyl aldehyde is 1:0.8, then enter micro passage reaction C2(internal diameter: 5mm) continuation reaction 30min, the product obtaining enters the threeway of micro mixer B3(T-type, internal diameter: 1mm) with pump into ammonium chloride solution at thermostat container D2(25 ℃ by syringe pump A3) in react, then enter micro passage reaction C3(internal diameter: 0.5mm) continue reaction 10s enter product-collecting bottle E.Product G C analyzes transformation efficiency 47%, 1-phenyl-2-propargyl alcohol selectivity 96%.
Embodiment 6
As shown in the figure: ethylmagnesium bromide is injected falling liquid film micro-structured reactor B1(length x width by high pressure syringe pump A1: 300 × 100 μ m) be metered into acetylene gas by F and react, ethylmagnesium bromide is than acetylene gas velocity ratio 1:25, at thermostat container D1(0 ℃) in there is Ge Shi permutoid reaction, enter micro passage reaction C1(internal diameter: 10mm) continuation reaction 30min, product ethynyl bromination magnesium pumps into the threeway of micro mixer B2(T-type by ram pump A4, internal diameter: 1mm) with the tetrahydrofuran (THF) mixed solution (0.5mol/L) that is pumped into phenyl aldehyde by high pressure syringe pump A2 at thermostat container D2(25 ℃) in mix, the mol ratio of Grignard reagent and phenyl aldehyde is 1:0.75, then enter micro passage reaction C2(internal diameter: 8mm) continuation reaction 30min, the product obtaining enters the threeway of micro mixer B3(T-type, internal diameter: 1mm) with pump into ammonium chloride solution at thermostat container D2(25 ℃ by syringe pump A3) in react, then enter micro passage reaction C3(internal diameter: 1mm) continue reaction 4min enter product-collecting bottle E.Product G C analyzes transformation efficiency 82%, 1-phenyl-2-propargyl alcohol selectivity 91%.
Embodiment 7
As shown in the figure: ethylmagnesium bromide is injected falling liquid film micro-structured reactor B1(length x width by high pressure syringe pump A1: 300 × 100 μ m) be metered into acetylene gas by F and react, ethylmagnesium bromide is than acetylene gas velocity ratio 1:25, at thermostat container D1(0 ℃) in there is Ge Shi permutoid reaction, enter micro passage reaction C1(internal diameter: 1mm) continuation reaction 10s, product ethynyl bromination magnesium pumps into the threeway of micro mixer B2(T-type by ram pump A4, internal diameter: 1mm) with the tetrahydrofuran (THF) mixed solution (0.5mol/L) that is pumped into phenyl aldehyde by high pressure syringe pump A2 at thermostat container D2(25 ℃) in mix, the mol ratio of Grignard reagent and phenyl aldehyde is 1:0.5, then enter micro passage reaction C2(internal diameter: 1mm) continuation reaction 20s, the product obtaining enters the threeway of micro mixer B3(T-type, internal diameter: 1mm) with pump into ammonium chloride solution at thermostat container D2(25 ℃ by syringe pump A3) in react, then enter micro passage reaction C3(internal diameter: 1mm) continue reaction 2min enter product-collecting bottle E.Product G C analyzes transformation efficiency 100%, 1-phenyl-2-propargyl alcohol selectivity 94%.
Embodiment 8
As shown in the figure: ethylmagnesium bromide is injected micro mixer B1(V2 by high pressure syringe pump A1, IMM, Germany) be metered into acetylene gas by F and react, ethylmagnesium bromide is than acetylene gas velocity ratio 1:25, at thermostat container D1(0 ℃) in there is Ge Shi permutoid reaction, enter micro passage reaction C1(internal diameter: 1mm) continuation reaction 10s, product ethynyl bromination magnesium pumps into the threeway of micro mixer B2(T-type by ram pump A4, internal diameter: 1mm) with the tetrahydrofuran (THF) mixed solution (0.5mol/L) that is pumped into phenyl aldehyde by high pressure syringe pump A2 at thermostat container D2(25 ℃) in mix, the mol ratio of Grignard reagent and phenyl aldehyde is 1:0.5, then enter micro passage reaction C2(internal diameter: 1mm) continuation reaction 20s, the product obtaining enters the threeway of micro mixer B3(T-type, internal diameter: 1mm) with pump into ammonium chloride solution at thermostat container D2(25 ℃ by syringe pump A3) in react, then enter micro passage reaction C3(internal diameter: 1mm) continue reaction 2min enter product-collecting bottle E.Product G C analyzes transformation efficiency 100%, 1-phenyl-2-propargyl alcohol selectivity 75%.
Embodiment 9
As shown in the figure: ethylmagnesium bromide is injected the threeway of micro mixer B1(T-type by high pressure syringe pump A1, internal diameter: 10mm) be metered into acetylene gas by F and react, ethylmagnesium bromide is than acetylene gas velocity ratio 1:25, at thermostat container D1(0 ℃) in there is Ge Shi permutoid reaction, enter micro passage reaction C1(internal diameter: 1mm) continuation reaction 10s, product ethynyl bromination magnesium pumps into the threeway of micro mixer B2(T-type by ram pump A4, internal diameter: 1mm) with the tetrahydrofuran (THF) mixed solution (0.5mol/L) that is pumped into phenyl aldehyde by high pressure syringe pump A2 at thermostat container D2(25 ℃) in mix, the mol ratio of Grignard reagent and phenyl aldehyde is 1:0.5, then enter micro passage reaction C2(internal diameter: 1mm) continuation reaction 20s, the product obtaining enters the threeway of micro mixer B3(T-type, internal diameter: 1mm) with pump into ammonium chloride solution at thermostat container D2(25 ℃ by syringe pump A3) in react, then enter micro passage reaction C3(internal diameter: 1mm) continue reaction 2min enter product-collecting bottle E.Product G C analyzes transformation efficiency 100%, 1-phenyl-2-propargyl alcohol selectivity 58%.
Embodiment 10
As shown in the figure: ethylmagnesium bromide is injected falling liquid film micro-structured reactor B1(length x width by high pressure syringe pump A1: 300 × 100 μ m) be metered into acetylene gas by F and react, ethylmagnesium bromide is than acetylene gas velocity ratio 1:25, at thermostat container D1(0 ℃) in there is Ge Shi permutoid reaction, enter micro passage reaction C1(internal diameter: 1mm) continuation reaction 10s, product ethynyl bromination magnesium pumps into the threeway of micro mixer B2(T-type by ram pump A4, internal diameter: 1mm) with the tetrahydrofuran (THF) mixed solution (0.5mol/L) that is pumped into phenyl aldehyde by high pressure syringe pump A2 at thermostat container D2(25 ℃) in mix, the mol ratio of Grignard reagent and phenyl aldehyde is 1:0.5, then enter micro passage reaction C2(internal diameter: 1mm) continuation reaction 20s, the product obtaining enters the threeway of micro mixer B3(T-type, internal diameter: 1mm) with pump into ammonium chloride solution at thermostat container D2(25 ℃ by syringe pump A3) in react, then enter micro passage reaction C3(internal diameter: 1mm) continue reaction 2min enter product-collecting bottle E.Product G C analyzes transformation efficiency 99%, 1-phenyl-2-propargyl alcohol selectivity 90%.
Embodiment 11
As shown in the figure: ethylmagnesium bromide is injected falling liquid film micro-structured reactor B1(length x width by high pressure syringe pump A1: 300 × 100 μ m) be metered into acetylene gas by F and react, ethylmagnesium bromide is than acetylene gas velocity ratio 1:4, at thermostat container D1(0 ℃) in there is Ge Shi permutoid reaction, enter micro passage reaction C1(internal diameter: 1mm) continuation reaction 1min, product ethynyl bromination magnesium pumps into the threeway of micro mixer B2(T-type by ram pump A4, internal diameter: 1mm) with the tetrahydrofuran (THF) mixed solution (0.5mol/L) that is pumped into phenyl aldehyde by high pressure syringe pump A2 at thermostat container D2(25 ℃) in mix, the mol ratio of Grignard reagent and phenyl aldehyde is 1:0.5, then enter micro passage reaction C2(internal diameter: 1mm) continuation reaction 20s, the product obtaining enters the threeway of micro mixer B3(T-type, internal diameter: 1mm) with pump into ammonium chloride solution at thermostat container D2(25 ℃ by syringe pump A3) in react, then enter micro passage reaction C3(internal diameter: 1mm) continue reaction 2min enter product-collecting bottle E.Product G C analyzes transformation efficiency 99%, 1-phenyl-2-propargyl alcohol selectivity 59%.
Embodiment 12
As shown in the figure: ethylmagnesium bromide is injected falling liquid film micro-structured reactor B1(length x width by high pressure syringe pump A1: 300 × 100 μ m) be metered into acetylene gas by F and react, ethylmagnesium bromide is than acetylene gas velocity ratio 1:25, at thermostat container D1(-20 ℃) in there is Ge Shi permutoid reaction, enter micro passage reaction C1(internal diameter: 1mm) continuation reaction 2min, product ethynyl bromination magnesium pumps into the threeway of micro mixer B2(T-type by ram pump A4, internal diameter: 1mm) with the tetrahydrofuran (THF) mixed solution (0.5mol/L) that is pumped into phenyl aldehyde by high pressure syringe pump A2 at thermostat container D2(40 ℃) in mix, the mol ratio of Grignard reagent and phenyl aldehyde is 1:0.5, then enter micro passage reaction C2(internal diameter: 1mm) continuation reaction 20s, the product obtaining enters the threeway of micro mixer B3(T-type, internal diameter: 0.1mm) with pump into ammonium chloride solution at thermostat container D2(40 ℃ by syringe pump A3) in react, then enter micro passage reaction C3(internal diameter: 1mm) continue reaction 1min enter product-collecting bottle E.Product G C analyzes transformation efficiency 97%, 1-phenyl-2-propargyl alcohol selectivity 91%.
Embodiment 13
As shown in the figure: ethylmagnesium bromide is injected falling liquid film micro-structured reactor B1(length x width by high pressure syringe pump A1: 1200 × 400 μ m) be metered into acetylene gas by F and react, ethylmagnesium bromide is than acetylene gas velocity ratio 1:25, at thermostat container D1(30 ℃) in there is Ge Shi permutoid reaction, enter micro passage reaction C1(internal diameter: 1mm) continuation reaction 10s, product ethynyl bromination magnesium pumps into the threeway of micro mixer B2(T-type by ram pump A4, internal diameter: 1mm) with the tetrahydrofuran (THF) mixed solution (2mol/L) that is pumped into phenyl aldehyde by high pressure syringe pump A2 at thermostat container D2(20 ℃) in mix, the mol ratio of Grignard reagent and phenyl aldehyde is 1:0.5, then enter micro passage reaction C2(internal diameter: 1mm) continuation reaction 20s, the product obtaining enters the threeway of micro mixer B3(T-type, internal diameter: 1mm) with pump into ammonium chloride solution at thermostat container D2(20 ℃ by syringe pump A3) in react, then enter micro passage reaction C3(internal diameter: 1mm) continue reaction 2min enter product-collecting bottle E.Product G C analyzes transformation efficiency 99%, 1-phenyl-2-propargyl alcohol selectivity 64%.
Embodiment 14
As shown in the figure: allyl group bromination magnesium injects falling liquid film micro-structured reactor B1(length x width by high pressure syringe pump A1: 300 × 100 μ m) be metered into acetylene gas by F and react, ethylmagnesium bromide is than acetylene gas velocity ratio 1:25, at thermostat container D1(0 ℃) in there is Ge Shi permutoid reaction, enter micro passage reaction C1(internal diameter: 1mm) continuation reaction 10s, product ethynyl bromination magnesium pumps into the threeway of micro mixer B2(T-type by ram pump A4, internal diameter: 1mm) with the tetrahydrofuran (THF) mixed solution (2mol/L) that is pumped into phenyl aldehyde by high pressure syringe pump A2 at thermostat container D2(25 ℃) in mix, the mol ratio of Grignard reagent and phenyl aldehyde is 1:0.5, then enter micro passage reaction C2(internal diameter: 1mm) continuation reaction 20s, the product obtaining enters the threeway of micro mixer B3(T-type, internal diameter: 1mm) with pump into ammonium chloride solution at thermostat container D2(25 ℃ by syringe pump A3) in react, then enter micro passage reaction C3(internal diameter: 1mm) continue reaction 2min enter product-collecting bottle E.Product G C analyzes transformation efficiency 99%, 1-phenyl-2-propargyl alcohol selectivity 90%.
Embodiment 15
As shown in the figure: normal-butyl bromination magnesium injects falling liquid film micro-structured reactor B1(length x width by high pressure syringe pump A1: 600 × 200 μ m) be metered into acetylene gas by F and react, ethylmagnesium bromide is than acetylene gas velocity ratio 1:25, at thermostat container D1(0 ℃) in there is Ge Shi permutoid reaction, enter micro passage reaction C1(internal diameter: 1mm) continuation reaction 30s, product ethynyl bromination magnesium pumps into the threeway of micro mixer B2(T-type by ram pump A4, internal diameter: 1mm) with the normal hexane mixed solution (1mol/L) that is pumped into phenyl aldehyde by high pressure syringe pump A2 at thermostat container D2(25 ℃) in mix, the mol ratio of Grignard reagent and phenyl aldehyde is 1:0.5, then enter micro passage reaction C2(internal diameter: 1mm) continuation reaction 20s, the product obtaining enters the threeway of micro mixer B3(T-type, internal diameter: 1mm) with pump into ammonium chloride solution at thermostat container D2(25 ℃ by syringe pump A3) in react, then enter micro passage reaction C3(internal diameter: 1mm) continue reaction 2min enter product-collecting bottle E.Product G C analyzes transformation efficiency 90%, 1-phenyl-2-propargyl alcohol selectivity 74%.
Embodiment 16
As shown in the figure: methyl-magnesium-bromide injects falling liquid film micro-structured reactor B1(length x width by high pressure syringe pump A1: 300 × 100 μ m) be metered into acetylene gas by F and react, ethylmagnesium bromide is than acetylene gas velocity ratio 1:25, at thermostat container D1(0 ℃) in there is Ge Shi permutoid reaction, enter micro passage reaction C1(internal diameter: 1mm) continuation reaction 50s, product ethynyl bromination magnesium pumps into the threeway of micro mixer B2(T-type by ram pump A4, internal diameter: 1mm) with the ether mixed solution (5mol/L) that is pumped into phenyl aldehyde by high pressure syringe pump A2 at thermostat container D2(25 ℃) in mix, the mol ratio of Grignard reagent and phenyl aldehyde is 1:2, then enter micro passage reaction C2(internal diameter: 1mm) continuation reaction 20s, the product obtaining enters the threeway of micro mixer B3(T-type, internal diameter: 1mm) with pump into ammonium chloride solution at thermostat container D2(25 ℃ by syringe pump A3) in react, then enter micro passage reaction C3(internal diameter: 1mm) continue reaction 2min enter product-collecting bottle E.Product G C analyzes transformation efficiency 90%, 1-phenyl-2-propargyl alcohol selectivity 89%.
Embodiment 17
Press method described in embodiment 10, different is is raw materials usedly: aubepine.Product is through concentrated, and flash chromatography post separates, yield 95%, 1-p-methoxyphenyl-2-propargyl alcohol selectivity 99%.
1HNMR(400MHz,CDCl
3):δ7.48(d,2H,J=8.8Hz),6.91(d,2H,J=8.8Hz),5.42(d,1H,J=3.6Hz),3.81(d,3H,J=4.0Hz),2.66(d,1H,J=2.4Hz),2.24(d,1H,J=6.0Hz).
13C?NMR(100MHz,CDCl
3):δ159.8,132.4,128.0,114.0,83.7,74.6,64.0,55.3.
Embodiment 18
Press method described in embodiment 10, different is is raw materials usedly: p-bromobenzaldehyde.Product is through concentrated, and chromatography column separates, yield 87%, and 1-is to bromophenyl-2-propargyl alcohol selectivity 97%.
1H?NMR(400MHz,CDCl
3):δ
1H?NMR(400MHz,CDCl
3)7.80-7.78(m,1H),7.59-7.56(m,1H),7.40-7.36(m,1H),7.23-7.20(m,1H),5.82-5.80(m,1H),2.67(d,1H,J=2.4Hz),2.52(d,1H,J=5.6Hz).
13C?NMR(100MHz,CDCl
3):δ138.9,133.0,130.0,128.5,128.0,122.7,82.4,75.0,63.9.
Embodiment 19
Press method described in embodiment 10, different is is raw materials usedly: o-bromobenzaldehye.Product is through concentrated, and flash chromatography post separates, yield 92%, 1-o-bromophenyl-2-propargyl alcohol selectivity 98%.
1H?NMR(400MHz,CDCl
3):δ7.53-7.42(m,4H),5.43(dd,1H,J=2.0,4.0Hz),2.68(d,1H,J=2.4Hz),2.28(d,1H,J=6.0Hz).
13C?NMR(100MHz,CDCl
3):δ139.0,131.8,128.3,122.6,83.0,75.2,68.0,63.8,25.6.
Embodiment 20
Press method described in embodiment 10, different is is raw materials usedly: 4-chloro-benzaldehyde.Product is through concentrated, and flash chromatography post separates, yield 88%, 1-rubigan-2-propargyl alcohol selectivity 96%.
1H?NMR(400MHz,CDCl
3):δ7.48(d,2H,J=8.8Hz),7.35(d,2H,J=8.4Hz),5.43(s,1H),2.67(d,1H,J=2.4Hz),2.49(s,1H).
13C?NMR(100MHz,CDCl
3):δ138.4,134.4,128.8,128.0,83.0,75.2,63.7.
Embodiment 21
Press method described in embodiment 10, different is is raw materials usedly: p-Fluorobenzenecarboxaldehyde.Product is through concentrated, and flash chromatography post separates, yield 92%, and 1-is to fluorophenyl-2-propargyl alcohol selectivity 95%.
1H?NMR(400MHz,CDCl
3):δ7.54-7.51(m,2H),7.08-7.04(m,2H),5.44(s,1H),2.68(d,1H,J=2.0Hz),2.45(d,1H,J=3.2Hz).
13C?NMR(100MHz,CDCl
3):δ162.8(J=245.4Hz),135.8(J=3.3Hz),128.5(J=8.6Hz),115.5(J=21.7Hz),83.3,75.1,63.8.
Embodiment 22
Press method described in embodiment 10, different is is raw materials usedly: 3,4,5-Trimethoxybenzaldehyde.Product, through concentrated, separated and is obtained product, yield 92%, 1-(3,4,5-trimethoxy) phenyl-2-propargyl alcohol selectivity 93% by flash chromatography post.
1H?NMR(400MHz,CDCl
3):δ6.78(s,2H),5.42-5.40(m,1H),3.89(s,6H),3.85(s,3H),2.69(d,1H,J=2.4Hz),2.26(d,1H,J=6.4Hz).
13C?NMR(100MHz,CDCl
3):δ153.4,138.1,135.6,103.6,83.4,74.9,64.5,60.8,56.1.
Embodiment 23
Press method described in embodiment 10, different is is raw materials usedly: phenylacrolein.Product is through concentrated, and flash chromatography post separates and obtains product, yield 92%, 1-styryl-2-propargyl alcohol selectivity 98%.
1H?NMR(400MHz,CDCl
3):δ7.42-7.27(m,5H),6.83-6.80(dd,1H,J=14.8,0.8Hz),6.34-6.28(dd,1H,J=10.0,6.0Hz),5.09-5.05(m,1H),2.65(d,1H,J=2.4Hz),2.05-2.04(m,1H).
13C?NMR(100MHz,CDCl
3):δ135.9,132.3,128.6,128.2,127.4,126.8,82.7,74.6,62.7.
Embodiment 24
Press method described in embodiment 10, different is is raw materials usedly: 9-Fluorenone, the nucleophilic addition(Adn) residence time is 50min.Product is through concentrated, and flash chromatography post separates and obtains product, yield 90%, 1-(9H-fluorenyl)-2-propargyl alcohol selectivity 95%.
1H?NMR(400MHz,CDCl
3):δ7.72(d,2H,J=6.8Hz),7.62(d,2H,J=7.2Hz),7.43-7.34(m,4H),2.54(s,1H),2.48(s,1H).
13C?NMR(100MHz,CDCl
3):δ146.6,139.1,129.9,128.6,124.3,120.2,83.8,74.6,71.4.
Embodiment 25
Press method described in embodiment 10, different is is raw materials usedly: pimelinketone.Product is through extraction, concentrated, adds internal standard substance sym-trimethylbenzene, gas chromatographic analysis yield 98%, 1-ethynylcyclohexanol selectivity 92%.
Embodiment 27
Press method described in embodiment 10, different is is raw materials usedly: valeral.Product is through extraction, concentrated, adds internal standard substance sym-trimethylbenzene, gas chromatographic analysis yield 98%, 1-amyl group-2-propargyl alcohol selectivity 91%.
Embodiment 26
Press method described in embodiment 10, different is is raw materials usedly: acetone.Product is through extraction, concentrated, adds internal standard substance sym-trimethylbenzene, gas chromatographic analysis, 2-methyl-3-butyne-2-alcohol yield 91%, selectivity 93%.Embodiment 27
Press method described in embodiment 10, different is is raw materials usedly: cinnamophenone.Product, through concentrated, separated and is obtained product, yield 96%, 1-phenyl-1-styryl-2-propargyl alcohol selectivity 95% by flash chromatography post.
1H?NMR(400MHz,CDCl
3):δ7.41-7.24(m,8H),7.69-7.67(m,2H),6.97(d,1H,J=16.0Hz),6.39-6.35(m,1H),2.87(s,1H),2.65(s,1H).
13C?NMR(100MHz,CDCl
3):δ142.8,136.0,132.3,129.4,128.6,128.4,128.1,128.0,126.9,125.7,84.7,75.8,72.7.
Claims (10)
1. utilize micro-structured reactor to prepare a method for propargyl alcohol, its concrete steps are as follows:
(1) Ge Shi exchange: in micro-structured reactor, Ge Shi permutoid reaction occurs for acetylene gas and Grignard reagent;
(2) nucleophilic addition(Adn): in micro-structured reactor, by step (1) product and electrophilic reagent generation nucleophilic addition;
(3) hydrolysis reaction: in micro-structured reactor, step (2) product, through hydrating solution generation hydrolysis reaction, is obtained replacing the thick product of propargyl alcohol;
(4) replace the thick product of propargyl alcohol through separation, purification, obtain replacing propargyl alcohol.
2. the method for claim 1, is characterized in that described Grignard reagent is methyl-magnesium-bromide, ethylmagnesium bromide, normal-butyl bromination magnesium or allyl group bromination magnesium.
3. method as claimed in claim 2, is characterized in that described Grignard reagent is ethylmagnesium bromide or methyl-magnesium-bromide.
4. the method for claim 1, is characterized in that described electrophilic reagent is aldehydes or ketones solution, and the structural formula of aldehydes or ketones is as R
1c (O) R
2, wherein R
1for alkyl C
nh
2n+1(n=1~5) or aromatic base, aromatic base is p-methoxy-phenyl, bromophenyl, chloro-phenyl-, fluorophenyl, trimethoxyphenyl or styryl; R2 alkyl C
nh
2n+1(n=1~5) or aromatic base, aromatic base is p-methoxy-phenyl, bromophenyl, chloro-phenyl-, fluorophenyl, trimethoxyphenyl or styryl.
5. the method for claim 1, is characterized in that described hydrating solution is ammonium chloride, dilute hydrochloric acid, ammonium sulfate or ammonium nitrate.
6. the method for claim 1, is characterized in that the micro-structured reactor in step (1), (2) and (3) includes micro mixer and micro passage reaction, and micro mixer and micro passage reaction link together.
7. method as claimed in claim 6, is characterized in that described micro passage reaction passage internal diameter is 0.1~10mm; Micro mixer internal diameter is 0.021~10mm.
8. the synthetic method of replacement propargyl alcohol as claimed in claim 1, is characterized in that described Ge Shi permutoid reaction acetylene gas flow velocity and Grignard reagent velocity ratio are 4~300:1; The mol ratio of Grignard reagent and electrophilic reagent is 1:(0.5-1.2).
9. the method for claim 1, it is characterized in that the temperature of reaction in described step (1) is-20~30 ℃; Temperature of reaction in step (2) is 20~40 ℃; Temperature of reaction in step (3) is 20~40 ℃.
10. the method for claim 1, is characterized in that the described Ge Shi permutoid reaction time is 5s~30min; The nucleophilic addition residence time is 6s~50min; The hydrolysis reaction residence time is 10s~10min.
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Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101495488A (en) * | 2006-07-18 | 2009-07-29 | 隆萨股份公司 | Method fro grignard type reactions in microreactors |
US20090275627A1 (en) * | 2008-05-05 | 2009-11-05 | Allergan, Inc. | Alpha2b and alpha2c agonists |
CN102701911A (en) * | 2011-03-28 | 2012-10-03 | 河北百灵威超精细材料有限公司 | A method for purification and enhanced stability of alkynol compounds |
CN102993133A (en) * | 2013-01-08 | 2013-03-27 | 南京工业大学 | Method for preparing epoxy fatty acid methyl ester by one-step method through microreactor |
-
2014
- 2014-03-31 CN CN201410127669.7A patent/CN103896737A/en active Pending
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101495488A (en) * | 2006-07-18 | 2009-07-29 | 隆萨股份公司 | Method fro grignard type reactions in microreactors |
US20090275627A1 (en) * | 2008-05-05 | 2009-11-05 | Allergan, Inc. | Alpha2b and alpha2c agonists |
CN102701911A (en) * | 2011-03-28 | 2012-10-03 | 河北百灵威超精细材料有限公司 | A method for purification and enhanced stability of alkynol compounds |
CN102993133A (en) * | 2013-01-08 | 2013-03-27 | 南京工业大学 | Method for preparing epoxy fatty acid methyl ester by one-step method through microreactor |
Non-Patent Citations (2)
Title |
---|
李洪钟: "《过程工程 物质.能源.智慧》", 31 December 2010 * |
穆金霞等: "微通道反应器在合成反应中的应用", 《化学进展》 * |
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