CN112920232B - Method for realizing alkynyl functional modification of glucosinolate by utilizing micro-flow field reaction technology - Google Patents

Method for realizing alkynyl functional modification of glucosinolate by utilizing micro-flow field reaction technology Download PDF

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CN112920232B
CN112920232B CN202110148413.4A CN202110148413A CN112920232B CN 112920232 B CN112920232 B CN 112920232B CN 202110148413 A CN202110148413 A CN 202110148413A CN 112920232 B CN112920232 B CN 112920232B
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郭凯
刘杰
邱江凯
袁鑫
覃龙州
孙蕲
段秀
张欣鹏
吴蒙雨
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Abstract

The invention discloses a method for realizing alkynyl functional modification of glucosinolate by utilizing a micro-flow field reaction technology, which comprises the steps of respectively pumping a first reaction liquid containing the glucosinolate shown in a formula I and a second reaction liquid containing an alkynyl functional reagent into a micro-flow field reaction device for reaction at the same time, and collecting effluent liquid to obtain a reaction liquid containing an alkynyl functional product of the glucosinolate shown in a formula II. The invention is a brand-new method for realizing the alkynyl functional modification of the glucosinolate, and the alkynyl functional modification of the glucosinolate can be realized only by adding organic alkali into a reaction system. The method can realize alkynyl functional modification of the glucosinolate at room temperature without using a catalyst.

Description

Method for realizing alkynyl functional modification of glucosinolate by utilizing micro-flow field reaction technology
Technical Field
The invention belongs to the field of chemical synthesis, and particularly relates to a method for realizing alkynyl functional modification of glucosinolate by utilizing a micro-flow field reaction technology.
Background
Thioglucoside is called thioglucoside for short, is an important secondary metabolite in cruciferous vegetables, and can be divided into three major classes of aliphatic, aromatic and indole groups according to different side chain groups. According to the report of animal experiments on the antitumor effect of the glucosinolate degradation product, the glucosinolate has obvious inhibition effect on tumors, and the glucosinolate mixture has stronger antitumor activity. In view of the antitumor activity of glucosinolates and their degradation products and the prevention of canceration by eating rich foods containing glucosinolates, research on glucosinolates has attracted considerable interest in recent years.
At present, a method for realizing the functional modification of the glucosinolate alkynyl by utilizing a micro-flow field reaction technology is rarely reported. Emmanuel Magnier reported in 2019 that arylation of thioglycoside was achieved using nickel and photo-redox dual catalysis (org. Lett.2019,21, 5132-. Although this reaction can effectively carry out arylation of thioglycoside and has a good substrate range, a photocatalyst metal catalyst needs to be added to the reaction system. A method for carrying out the arylation of glucosinolates using glucosinolates and corresponding reagents under electrical conditions was reported by Samir Messaoudi in 2020 (chem. Commun.2020,56, 4464-4467). Although this reaction can achieve arylation of thioglycoside under mild conditions, the reaction requires no electricity and is uneconomical and the scale of synthesis is small. The existing method for modifying the thioglucoside in a functionalization way has the defects of high-price catalyst, low atom utilization rate, environmental friendliness and the like, and the application of the method in industrialization is limited due to the defects. Therefore, it is very interesting to develop a method for the modification of thioglycoside functionalization that is catalyst-free, mild in reaction conditions, environmentally friendly and easy to scale up.
Disclosure of Invention
The purpose of the invention is as follows: the invention aims to solve the technical problem of the prior art and provides a method for realizing alkynyl functional modification of glucosinolate by utilizing a micro-flow field reaction technology.
In order to solve the technical problem, the invention discloses a method for realizing alkynyl functional modification of glucosinolate by utilizing a micro-flow field reaction technology, as shown in figure 1, a first reaction liquid containing the glucosinolate shown in a formula I and a second reaction liquid containing an alkynyl functional reagent are respectively and simultaneously pumped into a micro-flow field reaction device for reaction, and effluent liquid is collected to obtain a reaction liquid containing an alkynyl functional product of the glucosinolate shown in a formula II;
Figure BDA0002931122970000021
wherein,
R 1 selected from-H, -Ac (acetyl) or-Bz (benzoyl), preferably-Ac (acetyl);
R 2 is selected from alkane, cycloalkane, aryl derivative or heterocyclic structure, preferably aryl or aryl derivative, more preferably phenyl, TIPS, 2,4, 6-trimethylphenyl, 3-methylphenyl, 2-methylphenyl, 4-tert-butylphenyl and 4-trifluoromethylphenyl.
Wherein the concentration of the glucosinolate in the first reaction solution is 0.05 to 1.0mmol/mL, preferably 0.1 to 0.5 mmol/mL.
Wherein the first reaction solution further comprises an organic base.
Wherein, the organic base includes but is not limited to 2, 6-di-tert-butyl pyridine, N, N-diisopropyl ethylamine, pyridine, triethylamine, N, N, N ', N' -tetramethyl ethylenediamine, 4-dimethylamino pyridine, 2, 6-dimethyl pyridine and triethylene diamine.
Wherein, in the first reaction solution, the molar ratio of the glucosinolate to the organic base is 1: 1 to 5.
Wherein the structural formula of the alkynyl functional reagent is shown as a formula III,
Figure BDA0002931122970000022
wherein R is 2 Is selected from alkane, cycloalkane, aryl derivative or heterocyclic structure, preferably aryl or aryl derivative, more preferably benzene ring, TIPS, 2,4, 6-trimethylphenyl, 3-methylphenyl, 2-methylphenyl, 4-tert-butylphenyl and 4-trifluoromethylphenyl.
Wherein, in the second reaction solution, the molar ratio of the glucosinolate to the alkynyl functional reagent is 1: 1-5, that is, the concentration of the alkynyl functional reagent is 0.05-2.0 mmol/mL, preferably 0.15-1.0 mmol/mL.
The solvent of the first reaction solution and the solvent of the second reaction solution are respectively and independently selected from 1, 4-dioxane, dichloromethane, 1, 2-dichloroethane, N-dimethyl propylene urea, N-dimethylformamide, N-dimethylacetamide, methanol, ethanol, acetonitrile, acetone, water, phosphate buffer, tetrahydrofuran and dimethyl sulfoxide or any combination of a plurality of solvents, and preferably is dimethyl sulfoxide.
As shown in fig. 2, the microfluidic field reaction device comprises a feed pump, a mixing module, a microchannel reactor and a receiver; wherein, the reaction liquid pumped by the feed pump flows into the microchannel reactor for reaction after being mixed by the mixing module.
Wherein the feeding pump is a bagging Leifu Fluid Technology Co.Ltd, (TYD01-01-CE type).
Wherein, the mixing module is a Y-shaped mixer or a T-shaped mixer, preferably the T-shaped mixer, and the inner diameter is 0.6 mm.
The microchannel reactor is of a pore channel structure, the number of pore channels is increased or decreased according to needs, and the pore channel structure is made of perfluoroalkoxy alkane (PFA) or polytetrafluoroethylene.
Wherein the inner diameter of the microchannel reactor is 0.5-1.0 mm, the length is 5-20 m, and the volume is 1-15.7 mL; the inner diameter is preferably 0.6mm and the volume is preferably 2.0 mL.
Wherein the pumping rate of the first reaction liquid and the second reaction liquid is 1: 1, the flow rate is 0.1-2.0 mL/min.
Wherein the reaction temperature is room temperature.
Wherein the reaction time is 30 s-2.6 h, preferably 1 min-60 min, more preferably 1 min-30 min, even more preferably 1 min-10 min, and most preferably 5.0 min.
Has the advantages that: compared with the prior art, the invention has the following advantages:
(1) the invention is a brand-new method for realizing the alkynyl functional modification of the glucosinolate, and the alkynyl functional modification of the glucosinolate can be realized only by adding organic alkali into a reaction system.
(2) The method can realize alkynyl functional modification of the glucosinolate at room temperature without using a catalyst.
(3) The invention overcomes the problem that the prior art needs to use a transition metal catalyst, and reduces the reaction cost and the energy consumption cost.
(4) The system related by the invention has no solid insoluble substances, has no blockage problem of micro-reaction pore channels, is simple to operate and high in safety, and overcomes the defects of the traditional method.
(5) Compared with the existing reaction system, the reaction system related by the invention has the advantages of shortened reaction time, improved reaction conversion rate and yield, and high reaction continuity, and is favorable for continuous and uninterrupted scale-up production.
(6) The conversion rate of the raw materials is 82% -95%, and the product yield can reach 69-85%.
Drawings
The foregoing and/or other advantages of the invention will become further apparent from the following detailed description of the invention when taken in conjunction with the accompanying drawings.
FIG. 1 is a schematic diagram of the reaction scheme of the present invention.
FIG. 2 is a diagram of a microfluidic field reactor device.
FIG. 3 is a hydrogen spectrum of (2R, 3R, 4S, 5R, 6S) -2- (acetoxymethyl) -6- ((phenylethynyl) thio) tetrahydro-2H-pyran-3, 4, 5-triacetic acid triester.
FIG. 4 is a carbon spectrum of (2R, 3R, 4S, 5R, 6S) -2- (acetoxymethyl) -6- ((phenylethynyl) thio) tetrahydro-2H-pyran-3, 4, 5-triacetoxy triester.
FIG. 5 is a hydrogen spectrum of (2R, 3R, 4S, 5R, 6S) -2- (acetoxymethyl) -6- ((((triisopropylsilyl) ethynyl) thio) tetrahydro-2H-pyran-3, 4, 5-triacetic acid triester.
FIG. 6 is a carbon spectrum of (2R, 3R, 4S, 5R, 6S) -2- (acetoxymethyl) -6- ((((triisopropylsilyl) ethynyl) thio) tetrahydro-2H-pyran-3, 4, 5-triacetic acid triester.
FIG. 7 is a hydrogen spectrum of (2R, 3R, 4S, 5R, 6S) -2- (acetoxymethyl) -6- ((m-phenylethynyl) thio) tetrahydro-2H-pyran-3, 4, 5-triacetic acid triester.
FIG. 8 is a carbon spectrum of (2R, 3R, 4S, 5R, 6S) -2- (acetoxymethyl) -6- ((m-phenylethynyl) thio) tetrahydro-2H-pyran-3, 4, 5-triacetic acid triester.
FIG. 9 is a hydrogen spectrum of (2R, 3R, 4S, 5R, 6S) -2- (acetoxymethyl) -6- ((m-tolylethylthio) thio) tetrahydro-2H-pyran-3, 4, 5-triacetic acid triester.
FIG. 10 is a carbon spectrum of (2R, 3R, 4S, 5R, 6S) -2- (acetoxymethyl) -6- ((m-tolylethylthio) thio) tetrahydro-2H-pyran-3, 4, 5-triacetic acid triester.
FIG. 11 is a hydrogen spectrum of (2R, 3R, 4S, 5R, 6S) -2- (acetoxymethyl) -6- ((o-tolylethylthio) thio) tetrahydro-2H-pyran-3, 4, 5-triacetic acid triester.
FIG. 12 is a carbon spectrum of (2R, 3R, 4S, 5R, 6S) -2- (acetoxymethyl) -6- ((o-tolylethylthio) thio) tetrahydro-2H-pyran-3, 4, 5-triacetic acid triester.
FIG. 13 is a hydrogen spectrum of triester of (2R, 3R, 4S, 5R, 6S) -2- (acetoxymethyl) -6- ((((4- (tert-butyl) phenyl) ethynyl) thio) tetrahydro-2H-pyran-3, 4, 5-triacetic acid.
FIG. 14 is a carbon spectrum of (2R, 3R, 4S, 5R, 6S) -2- (acetoxymethyl) -6- ((((4- (tert-butyl) phenyl) ethynyl) thio) tetrahydro-2H-pyran-3, 4, 5-triacetic acid triester.
FIG. 15 is a hydrogen spectrum of triester of (2R, 3R, 4S, 5R, 6S) -2- (acetoxymethyl) -6- ((((4- (trifluoromethyl) phenyl) ethynyl) thio) tetrahydro-2H-pyran-3, 4, 5-triacetic acid.
FIG. 16 is a triester carbon spectrum of (2R, 3R, 4S, 5R, 6S) -2- (acetoxymethyl) -6- ((((4- (trifluoromethyl) phenyl) ethynyl) thio) tetrahydro-2H-pyran-3, 4, 5-triacetic acid.
FIG. 17 is a fluorine spectrum of (2R, 3R, 4S, 5R, 6S) -2- (acetoxymethyl) -6- ((((4- (trifluoromethyl) phenyl) ethynyl) thio) tetrahydro-2H-pyran-3, 4, 5-triacetic acid triester.
Detailed Description
The experimental methods described in the following examples are all conventional methods unless otherwise specified; the reagents and materials are commercially available, unless otherwise specified.
In the following examples, the flow rates of the first reaction solution and the second reaction solution were the same.
Example 1
Figure BDA0002931122970000051
0.0728g (0.2mmol,1.0equiv.) of (2R, 3R, 4S, 5R, 6S) -2- (acetoxymethyl) -6-mercaptotetrahydro-2H-pyran-3, 4, 5-triacetate was weighed, dissolved in N, N-dimethylformamide, 43. mu.L of triethylamine (0.3mmol,1.5equiv.) was added to prepare 2mL of a solution, and the solution was loaded in a syringe as a first reaction solution. 0.1308g of alkynyl reagent (0.3mmol,1.5equiv.) was weighed and dissolved in N, N-dimethylformamide to prepare 2mL of solution, which was loaded in a syringe as a second reaction solution. The first reaction solution and the second reaction solution are simultaneously pumped into a micro-flow field reaction device, mixed by a mixer and then enter a micro-channel reactor for reaction (the inner diameter is 0.6mm, the length is 7m, and the volume is 2mL), the pumping flow rate is 0.2mL/min, and the reaction retention time is 5.0 min. After completion of the reaction, TLC was carried out, and the reaction mixture was extracted with ethyl acetate and saturated brine (3X 25mL), and the organic layers were combined, dried over anhydrous sodium sulfate, and the solvent was removed by distillation under the reduced pressure, followed by silica gel column chromatography (petroleum ether: ethyl acetate: 2: 1) to give 65.8mg of a final product with a yield of 71%. The characterization data are as follows (fig. 3, fig. 4): 1 H NMR(400MHz,Chloroform-d)δ7.53–7.47(m,2H),7.37–7.29(m,3H),5.36–5.25(m,2H),5.15(t,J＝9.6Hz,1H),4.63(d,J＝9.3Hz,1H),4.30–4.24(m,1H),4.22–4.16(m,1H),3.83–3.77(m,1H),2.11(s,3H),2.06(s,3H),2.03(d,J＝5.2Hz,6H). 13 C NMR(100MHz,Chloroform-d)δ170.7,170.2,169.4,169.1,132.1,128.9,128.3,122.6,97.1,84.4,76.5,73.9,72.5,69.8,67.8,62.0,20.7(3),20.6(9),20.6(2),20.5(9).HRMS(ESI)m/z：calcd for C 22 H 24 O 9 SNa[M+Na] + ：487.1032,found：487.1032.
Example 2
0.0728g (0.2mmol,1.0equiv.) of (2R, 3R, 4S, 5R, 6S) -2- (acetoxymethyl) -6-mercaptotetrahydro-2H-pyran-3, 4, 5-triacetate was weighed, dissolved in acetonitrile, 43. mu.L of triethylamine (0.3mmol,1.5equiv.) was added to prepare 2mL of a solution, and the solution was loaded in a syringe as a first reaction solution. 0.1308g of an alkynyl reagent (0.3mmol,1.5equiv.) was weighed, dissolved in 2mL of acetonitrile, and loaded in a syringe as a second reaction solution. The first reaction solution and the second reaction solution are simultaneously pumped into a micro-flow field reaction device, mixed by a mixer and then enter a micro-channel reactor for reaction (the inner diameter is 0.6mm, the length is 7m, and the volume is 2mL), the pumping flow rate is 0.2mL/min, and the reaction retention time is 5.0 min. After completion of the reaction, TLC was carried out, and the reaction mixture was extracted with ethyl acetate and saturated brine (3X 25mL), and the organic layers were combined, dried over anhydrous sodium sulfate, and the solvent was removed by distillation under the reduced pressure, followed by silica gel column chromatography (petroleum ether: ethyl acetate: 2: 1) to give 67.7mg of a final product with a yield of 73%.
Example 3
0.0728g (0.2mmol,1.0equiv.) of (2R, 3R, 4S, 5R, 6S) -2- (acetoxymethyl) -6-mercaptotetrahydro-2H-pyran-3, 4, 5-triacetate was weighed out and dissolved in dimethyl sulfoxide, 43. mu.L of triethylamine (0.3mmol,1.5equiv.) was added thereto to prepare 2mL of a solution, which was loaded in a syringe as a first reaction solution. 0.1308g of an alkynyl reagent (0.3mmol,1.5equiv.) was weighed, dissolved in 2mL of dimethyl sulfoxide, and loaded in a syringe as a second reaction solution. The first reaction solution and the second reaction solution are simultaneously pumped into a micro-flow field reaction device, mixed by a mixer and then enter a micro-channel reactor for reaction (the inner diameter is 0.6mm, the length is 7m, and the volume is 2mL), the pumping flow rate is 0.2mL/min, and the reaction retention time is 5.0 min. After completion of the reaction, TLC was performed, and the reaction solution was extracted with ethyl acetate and saturated brine (3X 25mL), and the organic layers were combined, dried over anhydrous sodium sulfate, and the solvent was removed by distillation under the reduced pressure, followed by silica gel column chromatography (petroleum ether: ethyl acetate: 2: 1) to obtain 75.2mg of a final product with a yield of 81%.
Example 4
0.0728g (0.2mmol,1.0equiv.) of (2R, 3R, 4S, 5R, 6S) -2- (acetoxymethyl) -6-mercaptotetrahydro-2H-pyran-3, 4, 5-triacetate was weighed, dissolved in dimethyl sulfoxide, and 35. mu.L of 2, 6-lutidine (0.3mmol,1.5equiv.) was added thereto to prepare 2mL of a solution, which was loaded into a syringe as a first reaction solution. 0.1308g of an alkynyl reagent (0.3mmol,1.5equiv.) was weighed, dissolved in 2mL of dimethyl sulfoxide, and loaded in a syringe as a second reaction solution. The first reaction solution and the second reaction solution are simultaneously pumped into a micro-flow field reaction device, mixed by a mixer and then enter a micro-channel reactor for reaction (the inner diameter is 0.6mm, the length is 7m, and the volume is 2mL), the pumping flow rate is 0.2mL/min, and the reaction retention time is 5.0 min. After completion of the reaction, TLC was carried out, and the reaction mixture was extracted with ethyl acetate and saturated brine (3X 25mL), and the organic layers were combined, dried over anhydrous sodium sulfate, and the solvent was removed by distillation under the reduced pressure, followed by silica gel column chromatography (petroleum ether: ethyl acetate: 2: 1) to give 65.9mg of a final product with a yield of 71%.
Example 5
0.0728g (0.2mmol,1.0equiv.) of (2R, 3R, 4S, 5R, 6S) -2- (acetoxymethyl) -6-mercaptotetrahydro-2H-pyran-3, 4, 5-triacetate was weighed out and dissolved in dimethyl sulfoxide, and 24. mu.L of pyridine (0.3mmol,1.5equiv.) was added thereto to prepare 2mL of a solution, which was loaded in a syringe as a first reaction solution. 0.1308g of an alkynyl reagent (0.3mmol,1.5equiv.) was weighed, dissolved in 2mL of dimethyl sulfoxide, and loaded in a syringe as a second reaction solution. The first reaction solution and the second reaction solution are simultaneously pumped into a micro-flow field reaction device, mixed by a mixer and then enter a micro-channel reactor for reaction (the inner diameter is 0.6mm, the length is 7m, and the volume is 2mL), the pumping flow rate is 0.2mL/min, and the reaction retention time is 5.0 min. After completion of the reaction, TLC was performed, and the reaction solution was extracted with ethyl acetate and saturated brine (3 × 25mL), and the organic layers were combined, dried over anhydrous sodium sulfate, and the solvent was removed by distillation under the reduced pressure, followed by silica gel column chromatography (petroleum ether: ethyl acetate ═ 2: 1) to obtain 68.7mg of a final product with a yield of 74%.
Example 6
3.64g (10mmol,1.0equiv.) of (2R, 3R, 4S, 5R, 6S) -2- (acetoxymethyl) -6-mercaptotetrahydro-2H-pyran-3, 4, 5-triacetate is weighed, dissolved in dimethyl sulfoxide, and 2.2mL of triethylamine (15mmol,1.5equiv.) is added to prepare 20mL of a solution, which is loaded in a syringe as a first reaction solution. 6.54g of an alkynyl reagent (15mmol,1.5equiv.) was weighed, dissolved in 20mL of dimethyl sulfoxide, and loaded in a syringe as a second reaction solution. The first reaction solution and the second reaction solution are simultaneously pumped into a micro-flow field reaction device, mixed by a mixer and then enter a micro-channel reactor for reaction (the inner diameter is 0.6mm, the length is 7m, and the volume is 2mL), the pumping flow rate is 0.2mL/min, and the reaction retention time is 5.0 min. After completion of the reaction, TLC was performed, and the reaction solution was extracted with ethyl acetate and saturated brine (3 × 150mL), and the organic layers were combined, dried over anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure, followed by silica gel column chromatography (petroleum ether: ethyl acetate ═ 2: 1) to obtain 3.66g of a final product with a yield of 79%.
Example 7
Figure BDA0002931122970000081
0.0728g (0.2mmol,1.0equiv.) of (2R, 3R, 4S, 5R, 6S) -2- (acetoxymethyl) -6-mercaptotetrahydro-2H-pyran-3, 4, 5-triacetate was weighed out and dissolved in dimethyl sulfoxide, 43. mu.L of triethylamine (0.3mmol,1.5equiv.) was added thereto to prepare 2mL of a solution, which was loaded in a syringe as a first reaction solution. 0.1101g of an alkynyl reagent (0.3mmol,1.5equiv.) was weighed, dissolved in 2mL of dimethyl sulfoxide, and loaded in a syringe as a second reaction solution. The first reaction solution and the second reaction solution are simultaneously pumped into a micro-flow field reaction device, mixed by a mixer and then enter a micro-channel reactor for reaction (the inner diameter is 0.6mm, the length is 7m, and the volume is 2mL), the pumping flow rate is 0.2mL/min, and the reaction retention time is 5.0 min. After completion of the reaction, TLC was carried out, and the reaction mixture was extracted with ethyl acetate and saturated brine (3X 25mL), and the organic layers were combined, dried over anhydrous sodium sulfate, and the solvent was removed by distillation under the reduced pressure, followed by silica gel column chromatography (petroleum ether: ethyl acetate: 2: 1) to give 88.1mg of a final product with a yield of 81%. The characterization data are as follows (fig. 5, fig. 6): 1 H NMR(400MHz,Chloroform-d)δ5.26(d,J＝4.1Hz,2H),5.10(d,J＝8.3Hz,1H),4.62–4.51(m,1H),4.31–4.22(m,1H),4.13(d,J＝12.1Hz,1H),3.76(d,J＝6.1Hz,1H),2.08(s,6H),2.02(d,J＝6.8Hz,6H),1.10(s,21H). 13 C NMR(100MHz,Chloroform-d)δ170.7,170.3,169.3,168.9,102.3,88.8,84.9,76.5,73.8,69.9,67.8,62.0,20.7,20.6(2),20.6(1),20.5(7),18.5(9),18.5(8),11.3.HRMS(ESI)m/z：calcd for C 25 H 40 SiO 9 SNa[M+Na] + ：567.2055,found：567.2023.
Example 8
Figure BDA0002931122970000082
0.0728g (0.2mmol,1.0equiv.) of (2R, 3R, 4S, 5R, 6S) -2- (acetoxymethyl) -6-mercaptotetrahydro-2H-pyran-3, 4, 5-triacetate was weighed out and dissolved in dimethyl sulfoxide, 43. mu.L of triethylamine (0.3mmol,1.5equiv.) was added thereto to prepare 2mL of a solution, which was loaded in a syringe as a first reaction solution. 0.0987g of an alkynyl reagent (0.3mmol,1.5equiv.) was weighed, dissolved in 2mL of dimethyl sulfoxide, and loaded in a syringe as a second reaction solution. The first reaction solution and the second reaction solution are simultaneously pumped into a micro-flow field reaction device, mixed by a mixer and then enter a micro-channel reactor for reaction (the inner diameter is 0.6mm, the length is 7m, and the volume is 2mL), the pumping flow rate is 0.2mL/min, and the reaction retention time is 5.0 min. After completion of the reaction, TLC was carried out, and the reaction mixture was extracted with ethyl acetate and saturated brine (3X 25mL), and the organic layers were combined, dried over anhydrous sodium sulfate, and the solvent was removed by distillation under the reduced pressure, followed by silica gel column chromatography (petroleum ether: ethyl acetate: 2: 1) to give 86.1mg of a final product with a yield of 85%. The characterization data are as follows (fig. 7, fig. 8): 1 H NMR(400MHz,Chloroform-d)δ6.86(s,2H),5.34–5.25(m,2H),5.11(t,J＝9.5Hz,1H),4.60(d,J＝9.3Hz,1H),4.31–4.25(m,1H),4.19–4.14(m,1H),3.82–3.77(m,1H),2.41(s,6H),2.28(s,3H),2.09(s,3H),2.04(d,J＝5.8Hz,6H),2.01(s,3H). 13 C NMR(100MHz,Chloroform-d)δ170.7,170.3,169.3,169.0,140.9,138.4,131.1,129.3,127.6,124.8,119.6,94.9,84.5,79.1,76.4,73.8,69.9,67.8,62.0,21.4,21.0,20.7(0),20.6(7),20.6(2),20.5(9).HRMS(ESI)m/z：calcd for C 25 H 30 O 9 SNa[M+Na] + ：529.1503,found：529.1482.
example 9
Figure BDA0002931122970000091
0.0728g (0.2mmol,1.0equiv.) of (2R, 3R, 4S, 5R, 6S) -2- (acetoxymethyl) -6-mercaptotetrahydro-2H-pyran-3, 4, 5-triacetate was weighed out and dissolved in dimethyl sulfoxide, 43. mu.L of triethylamine (0.3mmol,1.5equiv.) was added thereto to prepare 2mL of a solution, which was loaded in a syringe as a first reaction solution. 0.0903g of an alkynyl reagent (0.3mmol,1.5equiv.) was weighed, dissolved in 2mL of dimethyl sulfoxide, and loaded in a syringe as a second reaction solution. The first reaction solution and the second reaction solution are simultaneously pumped into a micro-flow field reaction device, mixed by a mixer and then enter a micro-channel reactor for reaction (the inner diameter is 0.6mm, the length is 7m, and the volume is 2mL), the pumping flow rate is 0.2mL/min, and the reaction retention time is 5.0 min. After completion of the reaction, TLC was performed, and the reaction solution was extracted with ethyl acetate and saturated brine (3 × 25mL), and the organic layers were combined, dried over anhydrous sodium sulfate, and the solvent was removed by distillation under the reduced pressure, followed by silica gel column chromatography (petroleum ether: ethyl acetate ═ 2: 1) to obtain 71.8mg of a final product with a yield of 75%. The characterization data are as follows (fig. 9, fig. 10): 1 H NMR(400MHz,Chloroform-d)δ7.31(d,J＝8.3Hz,2H),7.21(t,J＝7.5Hz,1H),7.15(d,J＝7.4Hz,1H),5.35–5.24(m,2H),5.15(t,J＝9.4Hz,1H),4.62(d,J＝9.1Hz,1H),4.30–4.23m,1H),4.22–4.15(m,1H),3.84–3.76(m,1H),2.34(s,3H),2.10(s,3H),2.06(s,3H),2.03(d,J＝5.1Hz,6H). 13 C NMR(100MHz,Chloroform-d)δ170.7,170.2,169.4,138.0,132.6,129.8,129.2,128.2,122.4,97.2,84.5,76.5,73.9,72.1,69.8,67.9,62.0,21.2,20.7(2),20.6(8),20.6(2),20.5(8).HRMS(ESI)m/z：calcd for C 23 H 26 O 9 SNa[M+Na] + ：501.1190,found：501.1162.
Example 10
Figure BDA0002931122970000101
0.0728g (0.2mmol,1.0equiv.) of (2R, 3R, 4S, 5R, 6S) -2- (acetoxymethyl) -6-mercaptotetrahydro-2H-pyran-3, 4, 5-triacetate was weighed out and dissolved in dimethyl sulfoxide, and 43. mu.L of triethylamine (0.3 mmol) was added1.5equiv.), 2mL of the solution was prepared and loaded in a syringe as a first reaction solution. 0.0903g of an alkynyl reagent (0.3mmol,1.5equiv.) was weighed, dissolved in 2mL of dimethyl sulfoxide, and loaded in a syringe as a second reaction solution. The first reaction solution and the second reaction solution are simultaneously pumped into a micro-flow field reaction device, mixed by a mixer and then enter a micro-channel reactor for reaction (the inner diameter is 0.6mm, the length is 7m, and the volume is 2mL), the pumping flow rate is 0.2mL/min, and the reaction retention time is 5.0 min. After completion of the reaction, TLC was carried out, and the reaction mixture was extracted with ethyl acetate and saturated brine (3X 25mL), and the organic layers were combined, dried over anhydrous sodium sulfate, and the solvent was removed by distillation under the reduced pressure, followed by silica gel column chromatography (petroleum ether: ethyl acetate: 2: 1) to give 73.6mg of a final product in 77% yield. The characterization data are as follows (fig. 11, fig. 12): 1 H NMR(400MHz,Chloroform-d)δ7.46(d,J＝7.5Hz,1H),7.27–7.18(m,2H),7.14(t,J＝7.2Hz,1H),5.36–5.25(m,2H),5.12(d,J＝9.4Hz,1H),4.62(d,J＝9.3Hz,1H),4.31–4.24(m,1H),4.22–4.15(m,1H),3.85–3.77(m,1H),2.46(s,3H),2.10(s,3H),2.07–2.00(m,9H). 13 C NMR(100MHz,Chloroform-d)δ170.7,170.2,169.3,169.0,140.7,132.3,129.5,128.8,125.6,122.5,96.0,84.4,76.5,76.1,73.8,69.9,67.8,62.0,20.7(3),20.7(0),20.6(7),20.6(2),20.5(8).HRMS(ESI)m/z：calcd for C 23 H 26 O 9 SNa[M+Na] + ：501.1190,found：501.1167.
example 11
Figure BDA0002931122970000111
0.0728g (0.2mmol,1.0equiv.) of (2R, 3R, 4S, 5R, 6S) -2- (acetoxymethyl) -6-mercaptotetrahydro-2H-pyran-3, 4, 5-triacetate was weighed out and dissolved in dimethyl sulfoxide, 43. mu.L of triethylamine (0.3mmol,1.5equiv.) was added thereto to prepare 2mL of a solution, which was loaded in a syringe as a first reaction solution. 0.1029g of an alkynyl reagent (0.3mmol,1.5equiv.) was weighed, dissolved in 2mL of dimethyl sulfoxide, and loaded in a syringe as a second reaction solution. Pumping the first reaction liquid and the second reaction liquid into a micro-flow field reaction device simultaneously, and mixing by a mixer Then the mixture enters a microchannel reactor for reaction (the inner diameter is 0.6mm, the length is 7m, and the volume is 2mL), the pumping flow rate is 0.2mL/min, and the reaction residence time is 5.0 min. After completion of the reaction, TLC was performed, and the reaction solution was extracted with ethyl acetate and saturated brine (3 × 25mL), and the organic layers were combined, dried over anhydrous sodium sulfate, and the solvent was removed by distillation under the reduced pressure, followed by silica gel column chromatography (petroleum ether: ethyl acetate ═ 2: 1) to obtain 78.0mg of a final product with a yield of 75%. The characterization data are as follows (fig. 13, fig. 14): 1 H NMR(400MHz,Chloroform-d)δ7.45(d,J＝8.3Hz,2H),7.35(d,J＝8.3Hz,2H),5.36–5.24(m,2H),5.13(t,J＝9.5Hz,1H),4.62(d,J＝9.3Hz,1H),4.29–4.23(m,1H),4.21–4.15(m,1H),3.83–3.76(m,1H),2.11(s,3H),2.06(s,3H),2.03(d,J＝5.9Hz,6H),1.31(s,9H). 13 C NMR(100MHz,Chloroform-d)δ170.7,170.2,169.3,169.0,152.4,132.1,125.4,119.6,97.3,84.5,76.5,73.9,71.6,69.8,67.9,62.0,34.9,31.1,20.7(4),20.6(9),20.6(2),20.5(8).HRMS(ESI)m/z：calcd for C 26 H 32 O 9 SNa[M+Na] + ：543.1659,found：543.1628.
example 12
Figure BDA0002931122970000112
0.0728g (0.2mmol,1.0equiv.) of (2R, 3R, 4S, 5R, 6S) -2- (acetoxymethyl) -6-mercaptotetrahydro-2H-pyran-3, 4, 5-triacetate was weighed out and dissolved in dimethyl sulfoxide, 43. mu.L of triethylamine (0.3mmol,1.5equiv.) was added thereto to prepare 2mL of a solution, which was loaded in a syringe as a first reaction solution. 0.1065g of an alkynyl reagent (0.3mmol,1.5equiv.) was weighed, dissolved in 2mL of dimethyl sulfoxide, and loaded in a syringe as a second reaction solution. The first reaction solution and the second reaction solution are simultaneously pumped into a micro-flow field reaction device, mixed by a mixer and then enter a micro-channel reactor for reaction (the inner diameter is 0.6mm, the length is 7m, and the volume is 2mL), the pumping flow rate is 0.2mL/min, and the reaction retention time is 5.0 min. After completion of the reaction, TLC was performed, and the reaction mixture was extracted with ethyl acetate and saturated brine (3X 25mL), and the organic layers were combined, dried over anhydrous sodium sulfate, and the solvent was removed by distillation under the reduced pressure and passed through a silica gel column The product was separated out (petroleum ether: ethyl acetate 2: 1) to give 88.4mg of the final product in 83% yield. The characterization data were as follows (fig. 15, 16, 17): 1 H NMR(400MHz,Chloroform-d)δ7.59(s,4H),5.38–5.25(m,2H),5.16(t,J＝9.5Hz,1H),4.64(d,J＝9.4Hz,1H),4.31–4.24(m,1H),4.19(d,J＝11.4Hz,1H),3.86–3.78(m,1H),2.10(s,3H),2.08–2.01(m,9H). 13 C NMR(100MHz,Chloroform-d)δ170.6,170.2,169.4,169.0,132.0,130.3(q,J＝32.5Hz,1C),126.4,125.3(q,J＝3.7Hz,2C),123.8(q,J＝270.8Hz,1C),95.9,84.2,76.6,75.8,73.8,69.7,67.8,61.9,20.7,20.6(3),20.5(8),20.5(5). 19 F NMR(376MHz,Chloroform-d)δ62.88.HRMS(ESI)m/z：calcd for C 23 H 23 F 3 O 9 SNa[M+Na] + ：555.0907,found：555.0876.
comparative example 1
0.0728g of (2R, 3R, 4S, 5R, 6S) -2- (acetoxymethyl) -6-mercaptotetrahydro-2H-pyran-3, 4, 5-triacetate, 0.1308g of an alkynyl reagent (0.3mmol,1.5equiv.) were weighed into a Schlenk reaction tube, and after replacing argon three times, 2mL of dimethyl sulfoxide and 43. mu.L of triethylamine (0.3mmol,1.5equiv.) were added. After 3 hours of reaction at room temperature, TLC detection was performed, the reaction solution was extracted with ethyl acetate and saturated brine (3X 25mL), the organic layers were combined, dried over anhydrous sodium sulfate, the solvent was removed by distillation under the reduced pressure, and column chromatography on silica gel (petroleum ether: ethyl acetate: 2: 1) was performed to give 69.6mg of a final product with a yield of 75%.
The invention provides a thought and a method for realizing alkynyl functional modification of glucosinolate by utilizing a micro-flow field reactor, and a method and a way for realizing the technical scheme are many, the above description is only a preferred embodiment of the invention, and it should be noted that, for a person skilled in the art, a plurality of improvements and decorations can be made without departing from the principle of the invention, and the improvements and decorations should also be regarded as the protection scope of the invention. All the components not specified in the present embodiment can be realized by the prior art.

Claims (8)

1. A method for realizing alkynyl functional modification of glucosinolate by utilizing a micro-flow field reaction technology is characterized in that a first reaction liquid containing glucosinolate shown in a formula I and organic base and a second reaction liquid containing alkynyl functional reagent shown in a formula III are respectively and simultaneously pumped into a micro-flow field reaction device for reaction, and effluent liquid is collected to obtain a reaction liquid containing alkynyl functional products of the glucosinolate shown in a formula II;
Figure FDA0003730247470000011
wherein,
R 1 is selected from-H, -Ac or-Bz;
R 2 selected from alkane, cyclane, benzene ring, triisopropyl silicon, 2,4, 6-trimethylphenyl, 3-methylphenyl, 2-methylphenyl, 4-tert-butylphenyl and 4-trifluoromethylphenyl.
2. The method according to claim 1, wherein the concentration of thioglucoside in the first reaction solution is 0.05 to 1.0 mmol/mL.
3. The method according to claim 1, wherein the molar ratio of the glucosinolate to the organic base in the first reaction solution is 1: 1 to 5.
4. The method according to claim 1, wherein the concentration of the alkynyl functional reagent in the second reaction solution is 0.05 to 2.0 mmol/mL.
5. The method according to claim 1, wherein the solvent of the first reaction solution and the second reaction solution is independently selected from 1, 4-dioxane, dichloromethane, 1, 2-dichloroethane, N-dimethylpropyleneurea, N-dimethylformamide, N-dimethylacetamide, methanol, ethanol, acetonitrile, acetone, water, phosphate buffer, tetrahydrofuran, and dimethyl sulfoxide, or any combination thereof.
6. The method of claim 1, wherein the pumping rates of the first reaction solution and the second reaction solution are 1: 1.
7. the method of claim 1, wherein the temperature of the reaction is room temperature.
8. The method according to claim 1, wherein the reaction time is 30s to 2.6 h.
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