CN110372506B - Novel method for realizing visible light catalytic asymmetric oxidation by utilizing microreactor - Google Patents
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Abstract
The invention belongs to the field of flow chemistry, and provides a novel method for realizing visible light catalytic asymmetric oxidation by using a microreactor. The method utilizes a microreactor to realize continuous preparation of chiral alpha-hydroxy-beta-dicarbonyl compounds by utilizing a cinchona alkaloid derived phase transfer catalyst and catalyzing asymmetric photocatalytic oxidation of beta-dicarbonyl compounds by taking oxygen as an oxidant under the condition of no additional photosensitizer or introduced photosensitive groups under the condition of visible light. The method has the advantages that the reaction temperature is-15-30 ℃, the reaction retention time is 5-200 min, and 100% of substrate conversion rate and enantioselectivity of more than 70% can be realized. The method has the advantages of mild reaction conditions, continuous reaction, catalyst with double-functionalization characteristics of a chiral catalytic center and a photosensitive center, no amplification effect and easy industrialization.
Description
Technical Field
The invention belongs to the field of flow chemistry, and relates to a novel method for realizing visible light catalytic asymmetric oxidation by utilizing a microreactor.
Background
At present, visible light can be applied to synthesis of chiral alpha-hydroxy-beta-dicarbonyl compounds, and the compounds generally exist in nature, and particularly, methyl indoxacarb attracts attention as an important intermediate of indoxacarb. In 2012, we reported that Tetraphenylporphyrin (TPP) was used as a photosensitizer to activate oxygen in the air under visible light to catalyze asymmetric photocatalytic oxidation of β -dicarbonyl compounds using cinchona-derived phase transfer catalyst (chem. asian. j.2012,7, 2019-2023). Thereafter, patent CN106045985A and patent CN107899611A report that an organic visible light catalyst is combined with a chiral organic catalyst to form a bifunctional metal organic catalyst or a bifunctional organic catalyst, respectively. However, in both of these catalysts, a photosensitive group needs to be additionally introduced into the catalyst, and the introduction of the photosensitive group not only increases the synthesis steps of the catalyst, but also increases the reaction cost.
According to the Bouguer-Lambert-Beer law, photocatalytic reactions are significantly limited in scale-up production using the "volume up" strategy. In addition, the introduction of air or oxygen in the photocatalytic oxidation reaction system can cause great potential safety hazard in the actual production. A micro-reactor or micro-structure reactor or micro-channel reactor is a device in which chemical reactions occur with characteristic dimensions of less than 1mm, and a micro-reactor is a generic term for chemical equipment such as micro-controllers, mixers, heat exchangers, reactors, and the like. The microreactor has the following characteristics: (1) extremely high mass and heat transfer efficiency; (2) continuous flow operation; (3) no amplification effect; (4) the safety is high. Therefore, the method provides that the catalyst has the characteristics of a catalytic center and a photosensitive center under the condition of visible light by using the microreactor and under the condition of no external photosensitizer or introduced photosensitive groups, so that the chiral alpha-hydroxy-beta-dicarbonyl compound is continuously prepared, the operation process is simplified, the catalyst cost is reduced, the reaction selectivity and the reaction yield are improved, and the continuous production, stable amplification and safe production process are realized.
Disclosure of Invention
The invention provides a novel method for realizing visible light catalytic asymmetric oxidation by utilizing a microreactor. The method utilizes a microreactor to realize the continuous preparation of the chiral alpha-hydroxy-beta-dicarbonyl compound by utilizing a phase transfer catalyst derived from cinchona alkaloid and catalyzing the asymmetric photocatalytic oxidation of the beta-dicarbonyl compound by taking air or oxygen as an oxidant under the condition of no additional photosensitizer or introduced photosensitive groups. The method realizes that the catalyst simultaneously has dual functions of a chiral catalytic center and a photosensitive center, reduces the reaction cost, simultaneously aims to overcome the reaction limitation existing in the intermittent volume amplification in the photochemical reaction and the potential safety hazard caused by the introduction of a large amount of oxygen in the reaction, and has the advantages of mild reaction conditions, continuous reaction, no amplification effect, safe process and easy industrialization.
In order to achieve the purpose of the invention, the technical scheme of the invention is as follows:
a novel method for realizing visible light catalytic asymmetric oxidation by utilizing a microreactor. The method is realized by a microchannel reactor with a gas-liquid mixing function, a reaction system in the reactor is a three-phase reaction system of a gas phase, a water phase and an organic phase, a phase transfer catalyst derived from cinchona alkaloid is utilized under the condition of visible light irradiation, the reaction temperature is-15-30 ℃, the reaction residence time is 5-200 min, and the visible light activates oxygen to realize continuous oxidation so as to prepare the chiral alpha-hydroxy-beta-dicarbonyl compound from the beta-dicarbonyl compound; the visible light wavelength in the microchannel reactor is 300-800nm, and the pressure in the reactor is 0-6 bar. The flow rates of the three-phase fluid are respectively as follows: (1) the flow rate of the organic phase is 0.3-5 mL/min; (2) the flow rate of the water phase is 0.3-5 mL/min; (3) the flow rate of the gas phase is 1-15 mL/min.
The water phase is an aqueous solution of inorganic alkali or inorganic salt, wherein the mass concentration of the alkali or salt solution is 0.01-50%. The aqueous solution of inorganic base or inorganic salt comprises one or more of sodium carbonate, potassium carbonate, cesium carbonate, sodium hydroxide, potassium hydroxide, dipotassium hydrogen phosphate, potassium dihydrogen phosphate and the like. Cesium carbonate and dipotassium hydrogen phosphate are preferable.
The gas phase is air, pure oxygen and a mixture of oxygen and inert gas, wherein the proportion of the oxygen in the gas phase is 1.0-99.99%, and preferably 10-30%.
The organic phase is formed by dissolving a beta-dicarbonyl compound and a cinchona alkaloid derived phase transfer catalyst in an organic solvent according to a certain proportion and concentration, wherein the molar ratio of the beta-dicarbonyl compound to the cinchona alkaloid derived phase transfer catalyst is 0.1-50 mol%, and the concentration of the beta-dicarbonyl compound in the organic phase is 0.001-1 mmol/mL.
The solvent comprises aromatic hydrocarbon or alkane, the aromatic hydrocarbon comprises toluene, o-xylene, p-xylene, m-xylene, mesitylene, p-chlorotoluene, o-chlorotoluene and the like, and the alkane comprises dichloromethane, chloroform, carbon tetrachloride, petroleum ether, cyclohexane or ethyl acetate and the like. Preferably, the molar ratio of the beta-dicarbonyl compound to the cinchona-derived phase transfer catalyst is 5-20 mol%, the concentration of the beta-dicarbonyl compound in the organic phase is 0.001-0.1 mmol/mL, and the solvent is toluene or o-xylene.
The beta-dicarbonyl compound comprises Ia or Ib, and the reaction included in the method for preparing the chiral alpha-hydroxy-beta-dicarbonyl compound by photocatalytic oxidation of the beta-dicarbonyl compound comprises the following two reactions:
wherein: r10Is alkyl, cycloalkyl, aromatic ring or benzyl, n is 1 or 2; r11-R13Hydrogen atom, halogen, alkyl, alkoxy and cycloalkyl, which are the same or different; r14And R15Hydrogen atom, aromatic ring, alkyl group, cycloalkyl group, the same or different.
The cinchona alkaloid derived Phase Transfer Catalyst (PTC) has the following structure:
wherein R is1Is a hydroxyl group; r2Fluorine, chlorine, bromine, iodine; r3Aryl substituents such as phenyl, naphthyl and m-trifluoromethylphenyl; r4Aryl substituents such as vinyl, ethyl, styryl, p-trifluoromethylstyryl and the like; r5、R6、R7、R8And R9Is H, halogen, trifluoromethyl or methoxy, the five are the same or different. Preferably R1Is a hydroxyl group; r2Is bromine; r3Is phenyl, m-trifluoromethylphenyl; r4Preferably a vinyl group; r5、R6、R9Is H, R7、R8Is bromine.
The invention has the beneficial effects that: the invention effectively realizes that the phase transfer catalyst derived from cinchona alkaloid is utilized to realize the double functionalization of the catalyst with a chiral catalytic center and a photosensitive center under the condition of no external photosensitizer or photosensitive group introduction by utilizing the microreactor, thereby realizing the preparation of the chiral alpha-hydroxy-beta-dicarbonyl compound by catalyzing the asymmetric photocatalytic oxidation of the beta-dicarbonyl compound by taking oxygen as an oxidant, reducing the reaction cost, effectively overcoming the reaction limitation existing in the intermittent volume amplification in the photochemical reaction and the potential safety hazard caused by the introduction of a large amount of oxygen in the reaction, and effectively carrying out the serialization and the amplification of the reaction. In the reaction, oxidants such as peroxide or azaoxetane are not needed, oxygen in the air is used as the oxidant, and a photosensitizer or a photosensitive group is not needed to be additionally introduced into the reaction system, so that the synthesis cost and the reaction cost of the catalyst are greatly reduced. In addition, the method has the advantages of mild reaction conditions, continuous reaction, safe process, no amplification effect and easy industrialization.
Drawings
FIG. 1 is a flow chart of visible light photocatalytic asymmetric oxidation realized by using a microreactor in the invention.
FIG. 2 is the product IIa-1 of example 11H-NMR spectrum.
Detailed Description
Specific examples of the present invention will be described in detail below with reference to the technical solutions, but the process conditions are not limited to these examples.
Example 1: preparation of 2-hydroxy-1-indanone-2-carboxylic acid adamantyl ester
Weighing 0.031g (0.1mmol) of 1-indanone-2-carboxylic acid adamantyl ester (Ia-1), 0.0077g (0.01mmol, 10 mol%) of catalyst PTC-1, adding 10mL of toluene into a 20mL test tube, and completely dissolving the solid to obtain a bottle a; in addition, 50% K is provided2HPO4The solution is marked as a bottle B, the temperature of the whole reaction system is controlled to be 20 ℃, the pumping rate of the organic phase in the bottle a from the pump A is 1.5mL/min, the pumping rate of the alkali solution in the bottle B from the pump B is 1.5mL/min, the flow rate of the introduced oxygen (the oxygen content is 99.99%) is 3mL/min, the reaction pressure is 1bar, the light source is white light, and the retention time is 90 min. The starting material was completely converted and the organic phase was worked up to give the oxidation product IIa-1(0.031g, 95% yield, 82% ee).1H NMR (400MHz, Chloroform-d) δ 7.79(d, J ═ 7.7Hz,1H),7.65(td, J ═ 7.5,1.2Hz,1H),7.47(d, J ═ 7.7Hz,1H),7.41(t, J ═ 7.4Hz,1H),4.03(s,1H),3.66(d, J ═ 17.1Hz,1H),3.22(d, J ═ 17.1Hz,1H),2.18 to 2.08(m,3H),1.96(d, J ═ 3.0Hz,6H),1.59(t, J ═ 3.0Hz,6H), product IIa-1 (a) and/b 1 (c, c1The H-NMR spectrum is shown in figure 1:
example 2: the process for preparing 2-hydroxy-1-indanone-2-formic acid adamantine ester enlarges 10 times of volume
Weighing 0.31g (1mmol) of 1-indanone-2-carboxylic acid adamantyl (Ia-1) and 0.077g (0.1mmol, 10 mol%) of catalyst PTC-1, adding 100mL of toluene into a 200mL test tube, and completely dissolving the solid, and marking as a bottle a; in addition, 50% K is provided2HPO4The solution is marked as a bottle B, the temperature of the whole reaction system is controlled to be 20 ℃, the pumping rate of the organic phase in the bottle a from the pump A is 1.5mL/min, the pumping rate of the alkali solution in the bottle B from the pump B is 1.5mL/min, the flow rate of the introduced oxygen (the oxygen content is 99.99%) is 3mL/min, the reaction pressure is 1bar, the light source is white light, and the retention time is 90 min. The starting material was completely converted and the organic phase was worked up to give the oxidation product IIa-1(0.31g, 95% yield, 82% ee).
Example 3: preparation of 5-chloro-2-hydroxy-1-indanone-2-carboxylic acid adamantyl ester
Weighing 0.0344g (0.1mmol) of 5-chloro-1-indanone-2-carboxylic acid adamantyl ester (Ia-2) and 0.0008g (0.001mmol, 1 mol%) of catalyst PTC-2, adding 100mL of o-xylene into a 200mL test tube, and marking as a bottle a when the solid is completely dissolved; in addition, 20% K is provided2HPO4The solution is marked as a bottle B, the temperature of the whole reaction system is controlled to be 10 ℃, the pumping rate of the organic phase in the bottle a from the pump A is 0.5mL/min, the pumping rate of the alkali solution in the bottle B from the pump B is 0.5mL/min, the air flow rate is 1mL/min, the reaction pressure is 0bar (normal pressure), the light source is 300nm LEDs, and the retention time is 5 min. The starting material was completely converted and the organic phase was worked up to give the oxidation product IIa-2(0.0339g, 94% yield, 80% ee).
Example 4: preparation of 5-bromo-2-hydroxy-1-indanone-2-carboxylic acid adamantyl ester
Weighing 0.039g (0.1mmol) of 5-bromo-1-indanone-2-carboxylic acid adamantyl ester (Ia-3) and 0.0001g (0.0001mmol, 0.1 mol%) of catalyst PTC-3, adding 10mL of m-xylene into a 20mL test tube, and marking as a bottle a when the solid is completely dissolved; another configuration is 10% K2HPO4And (3) marking the solution as a bottle B, controlling the temperature of the whole reaction system to be-15 ℃, controlling the pumping rate of the organic phase in the bottle a from the pump A to be 5mL/min, controlling the pumping rate of the alkali solution in the bottle B from the pump B to be 5mL/min, introducing the air flow rate to be 15mL/min, controlling the reaction pressure to be 5bar, controlling the light source to be purple light, and keeping the reaction time for 10 min. The starting material was completely converted and the organic phase was worked up to give the oxidation product IIa-3(0.039g, 95% yield, 76% ee).
Example 5: preparation of 4-methoxy-2-hydroxy-1-indanone-2-carboxylic acid adamantyl ester
Weighing 0.034g (0.1mmol) of 4-methoxy-1-indanone-2-carboxylic acid adamantyl ester (Ia-4) and 0.004g (0.005mmol, 5 mol%) of catalyst PTC-4, adding 10mL of mesitylene into a 20mL test tube, and marking as a bottle a when the solid is completely dissolved; in addition, 5% K is provided2HPO4And (3) marking the solution as a bottle B, controlling the temperature of the whole reaction system to be 0 ℃, controlling the pumping rate of the organic phase in the bottle a from the pump A to be 5mL/min, controlling the pumping rate of the alkali solution in the bottle B from the pump B to be 5mL/min, introducing mixed gas of oxygen and nitrogen (the volume ratio of the oxygen is 1.0%), controlling the flow rate to be 15mL/min, controlling the reaction pressure to be 6bar, and keeping the light source to be blue light for 5 min. The starting material was completely converted and the organic phase was worked up to give the oxidation product IIa-4(0.035g, 98% yield, 84% ee).
Example 6: preparation of 5, 6-dimethoxy-2-hydroxy-1-indanone-2-carboxylic acid adamantyl ester
0.037g (0.1mmol) of 5, 6-dimethoxy-1-indanone-2-carboxylic acid adamantyl ester (Ia-5), 0.0091g (0.01mmol, 10 mol%) of catalyst PTC-5 were weighed out and put in a 20mL test tube, 5mL of ethyl acetate was added and the solid was completely dissolvedMarked as bottle a; additionally, 1% K is provided2HPO4The solution is marked as a bottle B, the temperature of the whole reaction system is controlled to be 30 ℃, the pumping rate of the organic phase in the bottle a from the pump A is 2mL/min, the pumping rate of the alkali solution in the bottle B from the pump B is 2mL/min, the flow rate of the mixed gas of oxygen and helium (the volume ratio of the oxygen is 10%) is 4mL/min, the reaction pressure is 0bar (normal pressure), the light source is 470nm LEDs, and the retention time is 20 min. The starting material was completely converted and the organic phase was worked up to give the oxidation product IIa-5(0.037g, 96% yield, 81% ee).
Example 7: preparation of 5-chloro-2-hydroxy-1-indanone-2-carboxylic acid adamantyl ester
Weighing 0.0344g (0.1mmol) of 5-chloro-1-indanone-2-carboxylic acid adamantyl ester (Ia-2), 0.0077g (0.01mmol, 10 mol%) of catalyst PTC-6, adding 1mL of toluene into a 10mL test tube, and marking as a bottle a when the solid is completely dissolved; additionally, 1% Cs2CO3And the solution is marked as a bottle B, the temperature of the whole reaction system is controlled to be 20 ℃, the pumping rate of the organic phase in the bottle a from the pump A is 1.5mL/min, the pumping rate of the alkali solution in the bottle B from the pump B is 1.5mL/min, the flow rate of introduced oxygen is 3mL/min, the reaction pressure is 1bar, the light source is blue light, and the retention time is 90 min. The starting material was completely converted and the organic phase was worked up to give the oxidation product IIa-1(0.0336g, 93% yield, 90% ee).
Example 8: process for preparing 5-chloro-2-hydroxy-1-indanone-2-carboxylic acid adamantine ester by amplifying by 100 times of volume
Weighing 3.44g (10mmol) of 5-chloro-1-indanone-2-carboxylic acid adamantyl (Ia-2) and 0.77g (1mmol, 10 mol%) of catalyst PTC-6, adding 100mL of toluene into a 200mL beaker, and completely dissolving the solid, and marking as a bottle a; additionally, 1% Cs2CO3The solution is marked as a bottle B, the temperature of the whole reaction system is controlled to be 20 ℃, the pumping rate of the organic phase in the bottle a from the pump A is 1.5mL/min, and the alkali solution in the bottle B is pumped from the pump BThe speed is 1.5mL/min, the flow rate of the introduced oxygen is 3mL/min, the reaction pressure is 1bar, the light source is blue light, and the retention time is 90 min. The starting material was completely converted and the organic phase was worked up to give the oxidation product IIa-2(3.355g, 93% yield, 90% ee).
Example 9: the process for preparing 5-chloro-2-hydroxy-1-indanone-2-carboxylic acid adamantine ester is amplified by 1000 times of volume
34.48g (100mmol) of 5-chloro-1-indanone-2-carboxylic acid adamantyl (Ia-2) and 7.7g (10mmol, 10 mol%) of catalyst PTC-6 are weighed and put into a 2L beaker, 1L of toluene is added, and the solid is completely dissolved and marked as a bottle a; additionally, 1% Cs2CO3And the solution is marked as a bottle B, the temperature of the whole reaction system is controlled to be 20 ℃, the pumping rate of the organic phase in the bottle a from the pump A is 1.5mL/min, the pumping rate of the alkali solution in the bottle B from the pump B is 1.5mL/min, the flow rate of introduced oxygen is 3mL/min, the reaction pressure is 1bar, the light source is blue light, and the retention time is 90 min. The starting material was completely converted and the organic phase was worked up to give the oxidation product IIa-2(33.58g, 93% yield, 90% ee).
Example 10: preparation of 2-hydroxy-1-indanone-2-carboxylic acid methyl ester
Weighing 0.019g (0.1mmol) of 1-indanone-2-methyl formate (Ia-6) and 0.043g (0.05mmol, 50 mol%) of catalyst PTC-7, adding 1mL of carbon tetrachloride into a 10mL test tube, and completely dissolving the solid to obtain a bottle a; in addition, 50% K is provided2HPO4The solution is marked as a bottle B, the temperature of the whole reaction system is controlled to be-15 ℃, the pumping rate of the organic phase in the bottle a from the pump A is 0.3mL/min, the pumping rate of the alkali solution in the bottle B from the pump B is 0.3mL/min, the flow rate of the introduced oxygen (the oxygen content is 99%) is 1mL/min, the reaction pressure is 3bar, the light source is red light, and the retention time is 60 min. The starting material was completely converted and the organic phase was worked up to give the oxidation product IIa-6(0.020g, 95% yield, 86% ee).
Example 9: preparation of p-methylphenyl 2-hydroxy-1-indanone-2-carboxylate
Weighing 0.27g (1mmol) of 1-indanone-2-carboxylic acid p-methylphenyl ester (Ia-7) and 0.23g (0.3mmol, 30 mol%) of catalyst PTC-8, adding 1mL of chloroform into a 10mL test tube, and completely dissolving the solid to obtain a bottle a; another configuration is 10% K2HPO4The solution is marked as a bottle B, the temperature of the whole reaction system is controlled to be 0 ℃, the pumping rate of the organic phase in the bottle a from the pump A is 1.5mL/min, the pumping rate of the alkali solution in the bottle B from the pump B is 1.5mL/min, the flow rate of the introduced oxygen (the oxygen content is 99.9%) is 3mL/min, the reaction pressure is 0.5bar, the light source is 600nm LEDs, and the retention time is 150 min. The starting material was completely converted and the organic phase was worked up to give the oxidation product IIa-7(0.26g, 91% yield, 85% ee).
Example 10: preparation of 2-hydroxy-1-tetralone-2-carboxylic acid adamantane ester
Weighing 0.32g (1mmol) of 1-tetralone-2-adamantyl formate (Ia-8) and 0.07g (0.1mmol, 10 mol%) of catalyst PTC-9, adding 1mL of dichloromethane into a 10mL test tube, and completely dissolving the solid to obtain a bottle a; additionally, 0.1% K is provided2HPO4The solution is marked as a bottle B, the temperature of the whole reaction system is controlled to be minus 5 ℃, the pumping rate of the organic phase in the bottle a from the pump A is 1.5mL/min, the pumping rate of the alkali solution in the bottle B from the pump B is 1.5mL/min, the flow rate of the mixed gas of oxygen and nitrogen (oxygen content is 50%) is 3mL/min, the reaction pressure is 2bar, the light source is yellow light, and the retention time is 200 min. The starting material was completely converted and the organic phase was worked up to give the oxidation product IIa-8(0.30g, 89% yield, 82% ee).
Example 11: preparation of 2-hydroxy-2- (4-methylpiperidine-1-carbonyl) -2, 3-dihydro-1H-indanone
Weighing 2.6g (10mmol) of 2- (4-methylpiperidine-1-carbonyl) -2, 3-dihydro-1H-indanone (Ib-1) and 0.009g (0.01mmol, 0.1 mol%) of catalyst PTC-10, adding 2mL of chloroform into a 10mL test tube, and marking as a bottle a when the solid is completely dissolved; in addition, 1% of Na is prepared2CO3The solution is marked as a bottle B, the temperature of the whole reaction system is controlled to be-10 ℃, the pumping rate of the organic phase in the bottle a from the pump A is 0.5mL/min, the pumping rate of the alkali solution in the bottle B from the pump B is 0.5mL/min, the flow rate of the introduced oxygen (the oxygen content is 99.99%) is 1.5mL/min, the reaction pressure is 5bar, the light source is 800nm LEDs, and the retention time is 200 min. The starting material was completely converted and the organic phase was worked up to give the oxidized product IIb-1(2.6g, 96% yield, 84% ee).
Example 12: preparation of 2-hydroxy-N-methyl-N-phenyl-2, 3-dihydro-1H-indanone-2-carboxamide
Weighing 0.027g (0.1mmol) of N-methyl-N-phenyl-2, 3-dihydro-1H-indanone-2-formamide (Ia-1) and 0.028g (0.05mmol and 50 mol%) of catalyst PTC-11, adding 50mL of petroleum ether into a 100mL test tube, and completely dissolving the solid to be marked as a bottle; in addition, 20% of Na is prepared2CO3And (3) recording the solution as a bottle B, controlling the temperature of the whole reaction system to be 5 ℃, controlling the pumping rate of the organic phase in the bottle a from the pump A to be 0.3mL/min, controlling the pumping rate of the alkali solution in the bottle B from the pump B to be 0.3mL/min, introducing oxygen at the flow rate of 1mL/min, controlling the reaction pressure to be 6bar, controlling the light source to be red light, and keeping the reaction time for 180 min. The starting material was completely converted and the organic phase was worked up to give the oxidation product IIa-1(0.026g, 93% yield, -78% ee).
Examples 1, 3-7, and 10-12 are reported-free C-2' modified cinchona-alkaloid phase transfer catalysts, and verify that the catalysts themselves have dual functionalization with a chiral catalytic center and a photosensitive center under the condition that no photosensitizer is added or no photosensitive group is introduced into the catalysts, thereby greatly reducing the synthesis cost and the reaction cost of the catalysts. Meanwhile, the examples also prove the application of the catalyst in catalyzing the photocatalytic asymmetric oxidation of the beta-dicarbonyl compound, and prove that the catalyst has a good substrate application range. In examples 1-2 and 7-9, it was verified that the same yield and enantioselectivity could be obtained with the same residence time under the condition of 10-1000 times amplification of the reaction volume using the microreactor, respectively, and the method is suitable for "amplification" of the reaction.
The above-mentioned embodiments only express the embodiments of the present invention, but not should be understood as the limitation of the scope of the invention patent, it should be noted that, for those skilled in the art, many variations and modifications can be made without departing from the concept of the present invention, and these all fall into the protection scope of the present invention.
Claims (7)
1. A method for realizing visible light catalytic asymmetric oxidation by utilizing a microreactor; the method is characterized in that: the method is realized by a microchannel reactor with a gas-liquid mixing function, a reaction system in the reactor is a three-phase reaction system of a gas phase, a water phase and an organic phase, a phase transfer catalyst derived from cinchona alkaloid is utilized under the condition of visible light irradiation, the reaction temperature is-15-30 ℃, the reaction residence time is 5-200 min, and the visible light activates oxygen to realize continuous oxidation so as to prepare the chiral alpha-hydroxy-beta-dicarbonyl compound from the beta-dicarbonyl compound; the visible light wavelength in the microchannel reactor is 300-800nm, and the pressure in the reactor is 0-6 bar;
the organic phase is formed by dissolving a beta-dicarbonyl compound and a cinchona alkaloid derived phase transfer catalyst in an organic solvent according to a certain proportion and concentration, wherein the molar ratio of the cinchona alkaloid derived phase transfer catalyst to the beta-dicarbonyl compound is 0.1-50%, and the concentration of the beta-dicarbonyl compound in the organic phase is 0.001-1 mmol/ml;
the water phase is an aqueous solution of inorganic alkali or inorganic salt, wherein the mass concentration of the alkali or salt solution is 0.01-50%;
the gas phase is a mixture of air, pure oxygen and inert gas prepared according to a certain proportion, wherein the proportion of the oxygen in the gas phase is 1.0-99.99%;
the structure of the cinchona alkaloid derived phase transfer catalyst PTC is as follows:
wherein R is1Is a hydroxyl group; r2Fluorine, chlorine, bromine, iodine; r3Is phenyl or naphthyl; r4Vinyl, ethyl, styryl, p-trifluoromethylstyryl; r5、R6、R7、R8And R9Is H, halogen, trifluoromethyl or methoxy, the five being identical or different;
the beta-dicarbonyl compound is Ia or IIb, and the method for preparing the chiral alpha-hydroxy-beta-dicarbonyl compound by photocatalytic oxidation of the beta-dicarbonyl compound comprises the following two reactions:
wherein: r10Is alkyl, cycloalkyl, aromatic ring or benzyl, n is 1 or 2; r11-R13Hydrogen atom, halogen, alkyl, alkoxy and cycloalkyl, which are the same or different; r14And R15Hydrogen atom, aromatic ring, alkyl group, cycloalkyl group, the same or different.
2. The method for preparing chiral alpha-hydroxy-beta-dicarbonyl compound by photocatalytic asymmetric oxidation according to claim 1, wherein: in the PTC structure of the cinchona-derived phase transfer catalyst, preferably, R2Is bromine; r3Is phenyl; r4Is a vinyl group; r5、R6、R9Is H, R7、R8Is bromine.
3. A method according to claim 1 or 2 for performing visible light photocatalytic asymmetric oxidation using a microreactor, characterized in that: the flow rates of the three-phase fluid are respectively as follows: (1) the flow rate of the organic phase is 0.3-5 mL/min; (2) the flow rate of the water phase is 0.3-5 mL/min; (3) the flow rate of the gas phase is 1-15 mL/min.
4. A process for the photocatalytic asymmetric oxidation of chiral α -hydroxy- β -dicarbonyl compounds according to claim 1 or 2, characterized in that: the water solution of inorganic alkali or inorganic salt comprises one or more of sodium carbonate, potassium carbonate, cesium carbonate, sodium hydroxide, potassium hydroxide, dipotassium hydrogen phosphate and potassium dihydrogen phosphate.
5. The method for preparing chiral alpha-hydroxy-beta-dicarbonyl compound by photocatalytic asymmetric oxidation according to claim 3, wherein: the water solution of inorganic alkali or inorganic salt comprises one or more of sodium carbonate, potassium carbonate, cesium carbonate, sodium hydroxide, potassium hydroxide, dipotassium hydrogen phosphate and potassium dihydrogen phosphate.
6. A process for the photocatalytic asymmetric oxidation of chiral α -hydroxy- β -dicarbonyl compounds according to claim 1, 2 or 5, characterized in that: the solvent comprises aromatic hydrocarbon or alkane, the aromatic hydrocarbon comprises toluene, o-xylene, p-xylene, m-xylene, mesitylene, p-chlorotoluene and o-chlorotoluene, and the alkane comprises dichloromethane, chloroform, carbon tetrachloride, petroleum ether, cyclohexane or ethyl acetate.
7. The method for preparing chiral alpha-hydroxy-beta-dicarbonyl compound by photocatalytic asymmetric oxidation according to claim 4, wherein: the solvent comprises aromatic hydrocarbon or alkane, the aromatic hydrocarbon comprises toluene, o-xylene, p-xylene, m-xylene, mesitylene, p-chlorotoluene and o-chlorotoluene, and the alkane comprises dichloromethane, chloroform, carbon tetrachloride, petroleum ether, cyclohexane or ethyl acetate.
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