CN110372506A - A method of new realizes visible light catalytic asymmetric oxidation using microreactor - Google Patents
A method of new realizes visible light catalytic asymmetric oxidation using microreactor Download PDFInfo
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Abstract
The invention belongs to flow chemical field, a kind of new method for realizing visible light catalytic asymmetric oxidation using microreactor is provided.This method is realized under visible light conditions using microreactor, utilize phase transfer catalyst derived from quinine, under conditions of without adding photosensitizer outside or introducing photosensitive group, using oxygen as oxidant, the asymmetric photochemical catalytic oxidation for being catalyzed beta-dicarbonyl compound continuously prepares chiral alpha-hydroxy-beta-dicarbonyl compound.Method reaction temperature of the invention is -15~30 DEG C, and reaction time is 5~200min, 100% the substrate transformation rate can be realized, the enantioselectivity greater than 70%.This method has reaction condition mild, and reaction is continuous, and catalyst has a difunctionalization characteristic of chiral catalysis center and photosensitive center simultaneously, no enlarge-effect and is easy to industrialized advantage.
Description
Technical field
The invention belongs to flow chemical field, it is related to the new utilization microreactor of one kind and realizes visible light catalytic asymmetry oxygen
The method of change.
Background technique
Currently, visible light to be to be applied to synthesis of chiral Alpha-hydroxy-beta-dicarbonyl compound, and this kind of compound is in nature
It is generally existing in boundary, especially indone methyl formate as indoxacarb important intermediate and be concerned.2012, Wo Menbao
Road utilizes quinine phase transfer catalyst, using tetraphenylporphyrin (TPP) as photosensitizer activating air under visible light
In oxygen, be catalyzed beta-dicarbonyl compound asymmetric photocatalysis oxidation reaction (Chem.Asian.J.2012,7,2019-
2023).Thereafter, patent CN106045985A and patent CN107899611A is reported a kind of by organic visible light catalytic respectively
Agent is combined with chiral organicatalyst, forms difunctional orgnometallic catalyst or difunctional organic catalyst.But this two
Kind catalyst requires to additionally introduce photosensitive group in the catalyst, and introduces the synthesis that photosensitive group not only increases catalyst
Step also increases the cost of reaction.
According to Bouguer-Lambert-Beer law, light-catalyzed reaction is amplified in the strategy of utilization " volume amplification "
It will receive apparent limitation when production.In addition being passed through for air or oxygen in actual production can in photocatalysis oxidation reaction system
Cause great security risk.And microreactor or micro-structured reactor or micro passage reaction are that a kind of chemical reaction occurs to exist
Device with the characteristic size lower than 1mm, microreactor is the chemical industry equipments such as microcontroller, mixer, heat exchanger, reactor
Common name.Microreactor has the following characteristics that (1) high mass-and heat-transfer efficiency；(2) continuous flowing operation；(3) it is imitated without amplification
It answers；(4) highly-safe.Therefore, it is proposed that being realized under visible light conditions using microreactor, add photosensitizer outside in nothing or draw
Under conditions of entering photosensitive group, makes catalyst while there is the characteristic of catalytic center and photosensitive center, to continuously prepare chirality
Alpha-hydroxy-beta-dicarbonyl compound simplifies operating process, reduces catalyst cost, improves reaction selectivity and reaction yield, real
Existing continuous production stablizes amplification and safety in production process.
Summary of the invention
The present invention provides a kind of new methods for realizing visible light catalytic asymmetric oxidation using microreactor.This method
It is realized under visible light conditions using microreactor, using phase transfer catalyst derived from quinine, without outer plus photosensitizer
Or introduce under conditions of photosensitive group, using air or oxygen as oxidant, it is catalyzed the asymmetric photocatalysis of beta-dicarbonyl compound
Oxidation continuously prepares chiral alpha-hydroxy-beta-dicarbonyl compound.The method achieve catalyst to have chiral catalysis center simultaneously
It is Bifunctionalized with photosensitive center, reaction cost is reduced, while being intended to overcome interval " volume amplification " in photochemical reaction to deposit
Reaction limitation, and security risk caused by being passed through of a large amount of oxygen in reaction, this method reaction condition is mild, and reaction connects
Continuous, no enlarge-effect, process safety is easy to industrialized advantage.
In order to achieve the above-mentioned object of the invention, the technical solution of the present invention is as follows:
A method of new realizes visible light catalytic asymmetric oxidation using microreactor.This method passes through with gas-liquid
The micro passage reaction of immixture realizes that the reaction system in reactor is the phase reaction body of gas phase, water phase, organic phase
System, under the conditions of radiation of visible light, using phase transfer catalyst derived from quinine, reaction temperature is -15~30 DEG C, reaction
Residence time is 5~200min, it is seen that photoactivation oxygen realizes that beta-dicarbonyl compound is prepared chiral Alpha-hydroxy-by continuous oxidation
Beta-dicarbonyl compound；The a length of 300-800nm of visible light wave in the micro passage reaction, 0~6bar of reactor pressure.Institute
The flow velocity for the three-phase fluid stated is respectively as follows: the flow velocity 0.3-5mL/min of (1) organic phase；(2) the flow velocity 0.3-5mL/min of water phase；
(3) the flow velocity 1-15mL/min of gas phase.
The water phase is the aqueous solution of inorganic base or inorganic salts, wherein alkali or salting liquid mass concentration be 0.01~
50%.The aqueous solution of the inorganic base or inorganic salts, including sodium carbonate, potassium carbonate, cesium carbonate, sodium hydroxide, potassium hydroxide,
One or more kinds of mixing of dipotassium hydrogen phosphate, potassium dihydrogen phosphate etc..Preferably cesium carbonate, dipotassium hydrogen phosphate.
The gas phase is the mixture of air, purity oxygen and oxygen and inert gas, wherein oxygen proportion in gas phase
1.0~99.99%, preferably 10~30%.
The organic phase be beta-dicarbonyl compound, phase transfer catalyst derived from quinine by a certain percentage with it is dense
Degree dissolution is in organic solvent, wherein the molar ratio of beta-dicarbonyl compound and phase transfer catalyst derived from quinine is
0.1~50mol%, the concentration of beta-dicarbonyl compound is 0.001~1mmol/mL in organic phase.
The solvent includes aromatic hydrocarbons or alkanes, and aromatic hydrocarbons include toluene, ortho-xylene, paraxylene, diformazan
Benzene, dimethylbenzene, mesitylene, p-chlorotoluene, ortho-chlorotolu'ene etc., alkanes include methylene chloride, chloroform, carbon tetrachloride, petroleum
Ether, hexamethylene or ethyl acetate etc..It is preferred that the molar ratio of phase transfer catalyst derived from beta-dicarbonyl compound and quinine
For 5~20mol%, the concentration of beta-dicarbonyl compound is 0.001~0.1mmol/mL in organic phase, and solvent is toluene, neighbour two
Toluene.
The beta-dicarbonyl compound includes Ia or Ib, and photochemical catalytic oxidation beta-dicarbonyl compound prepares chiral alpha-hydroxyl
The reaction for including in base-beta-dicarbonyl compound method includes following two:
Wherein: R10For alkyl, naphthenic base, aromatic ring or benzyl, n is 1 or 2；R11-R13For hydrogen atom, halogen, alkyl, alcoxyl
Base, naphthenic base, three are identical or different；R14And R15For hydrogen atom, aromatic ring, alkyl, naphthenic base, the two is identical or different.
Phase transfer catalyst derived from the quinine (PTC) structure is as follows:
Wherein, R1For hydroxyl；R2For fluorine, chlorine, bromine, iodine；R3For the substitution of the aryl such as phenyl, naphthalene, m-trifluoromethylphenyl
Base；R4For aryl substituents such as vinyl, ethyl, styryl, p-trifluoromethylstyrene bases；R5、R6、R7、R8And R9For H,
Halogen, trifluoromethyl or methoxyl group, five is identical or different.Preferably R1For hydroxyl；R2For bromine；R3For phenyl, m-trifluoromethyl
Phenyl；R4Preferably vinyl；R5、R6、R9For H, R7、R8For bromine.
It is realized using microreactor in visible light conditions the invention has the benefit that effectiveness of the invention is embodied in
Under, using phase transfer catalyst derived from quinine, under conditions of without adding photosensitizer outside or introducing photosensitive group, realization is urged
Agent has difunctionalization at chiral catalysis center and photosensitive center simultaneously, to realize using oxygen as oxidant, is catalyzed β-two
The asymmetric photochemical catalytic oxidation of carbonyls prepares chiral alpha-hydroxy-beta-dicarbonyl compound, reduces reaction cost, effectively
Overcome in photochemical reaction in the existing reaction limitation of interval " volume amplification " and reaction caused by being passed through of a large amount of oxygen
Security risk makes reaction can be carried out effectively serialization and amplification.It is not needed in reaction using peroxide or azepine oxa-
Oxidants such as cyclopropane, and use oxygen in air as oxidant, do not need to be added and additionally introduce in simultaneous reactions system
Photosensitizer or photosensitive group, to greatly reduce the synthesis cost and reaction cost of catalyst.In addition, this method reacts item
Part is mild, and reaction is continuous, process safety, no enlarge-effect and is easy to industrialized advantage.
Detailed description of the invention
Fig. 1 is the flow chart that the present invention realizes visible light catalytic asymmetric oxidation using microreactor.
Fig. 2 is 1 product IIa-1's of embodiment1H-NMR spectrum.
Specific embodiment
Specific embodiments of the present invention are described in detail below with reference to technical solution, but process conditions are not limited only to these implementations
Example.
Embodiment 1: preparation 2- hydroxide radical-1-indenone -2- formic acid Buddha's warrior attendant ester
Weigh 0.031g (0.1mmol) 1- indone -2- formic acid Buddha's warrior attendant ester (Ia-1), 0.0077g (0.01mmol,
10mL toluene is added in 20mL test tube in 10mol%) catalyst PTC-1, and solid is completely dissolved, and is denoted as a bottles；Another configuration 50%
K2HPO4Solution is denoted as b bottles, and for entire reaction system controlled at 20 DEG C, it is 1.5mL/ that a bottles of organic phases, which are pumped into rate from A,
It is 1.5mL/min that aqueous slkali, which is pumped into rate from B, in min, b bottles, and being passed through oxygen (oxygen content 99.99%) flow velocity is 3mL/
Min, reaction pressure 1bar, light source are white light, residence time 90min.Raw material converts completely, and organic phase obtains after post treatment
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), 2.18-2.08 (m, 3H), 1.96 (d, J
=3.0Hz, 6H), 1.59 (t, J=3.0Hz, 6H) product IIa-1's1H-NMR spectrum is as shown in Figure 1:
Embodiment 2: preparation 2- hydroxide radical-1-indenone -2- formic acid Buddha's warrior attendant ester technique amplifies 10 times of volumes
Weigh 0.31g (1mmol) 1- indone -2- formic acid Buddha's warrior attendant ester (Ia-1), 0.077g (0.1mmol, 10mol%) catalysis
100mL toluene is added in 200mL test tube in agent PTC-1, and solid is completely dissolved, and is denoted as a bottles；Another configuration 50%K2HPO4Solution,
B bottles are denoted as, for entire reaction system controlled at 20 DEG C, it is 1.5mL/min, alkali in b bottles that a bottles of organic phases, which are pumped into rate from A,
It is 1.5mL/min that solution, which is pumped into rate from B, and being passed through oxygen (oxygen content 99.99%) flow velocity is 3mL/min, reaction pressure
For 1bar, light source is white light, residence time 90min.Raw material converts completely, and organic phase obtains oxidation product IIa- after post treatment
1 (0.31g, 95%yield, 82%ee).
Embodiment 3: preparation 5- chlorine-2-hydroxyl -1- indone -2- formic acid Buddha's warrior attendant ester
Weigh the chloro- 1- indone -2- formic acid Buddha's warrior attendant ester (Ia-2) of 0.0344g (0.1mmol) 5-, 0.0008g (0.001mmol,
100mL ortho-xylene is added in 200mL test tube in 1mol%) catalyst PTC-2, and solid is completely dissolved, and is denoted as a bottles；Separately match
Set 20%K2HPO4Solution is denoted as b bottles, and controlled at 10 DEG C, a bottles of organic phases are pumped into rate from A and are entire reaction system
It is 0.5mL/min that aqueous slkali, which is pumped into rate from B, in 0.5mL/min, b bottles, and being passed through air velocity is 1mL/min, reaction pressure
For 0bar (normal pressure), light source is 300nm LEDs, residence time 5min.Raw material converts completely, and organic phase obtains after post treatment
Oxidation product IIa-2 (0.0339g, 94%yield, 80%ee).
Embodiment 4: the preparation bromo- 2- hydroxide radical-1-indenone -2- formic acid Buddha's warrior attendant ester of 5-
Weigh the bromo- 1- indone -2- formic acid Buddha's warrior attendant ester (Ia-3) of 0.039g (0.1mmol) 5-, 0.0001g (0.0001mmol,
10mL meta-xylene is added in 20mL test tube in 0.1mol%) catalyst PTC-3, and solid is completely dissolved, and is denoted as a bottles；Separately match
Set 10%K2HPO4Solution is denoted as b bottles, and controlled at -15 DEG C, a bottles of organic phases are pumped into rate from A and are entire reaction system
It is 5mL/min that aqueous slkali, which is pumped into rate from B, in 5mL/min, b bottles, and being passed through air velocity is 15mL/min, and reaction pressure is
5bar, light source are purple light, residence time 10min.Raw material converts completely, and organic phase obtains oxidation product IIa-3 after post treatment
(0.039g, 95%yield, 76%ee).
Embodiment 5: preparation 4- methoxyl group -2- hydroxide radical-1-indenone -2- formic acid Buddha's warrior attendant ester
Weigh 0.034g (0.1mmol) 4- methoxyl group -1- indone -2- formic acid Buddha's warrior attendant ester (Ia-4), 0.004g
10mL mesitylene is added in 20mL test tube in (0.005mmol, 5mol%) catalyst PTC-4, and solid is completely dissolved, is denoted as
A bottles；Another configuration 5%K2HPO4Solution is denoted as b bottles, and for entire reaction system controlled at 0 DEG C, a bottles of organic phases are pumped into speed from A
Rate is 5mL/min, and it is 5mL/min that aqueous slkali, which is pumped into rate from B, in b bottles, is passed through oxygen and nitrogen mixed gas (oxygen volume
Ratio 1.0%) flow velocity be 15mL/min, reaction pressure 6bar, light source is blue light, residence time 5min.Raw material converts completely,
Organic phase obtains oxidation product IIa-4 (0.035g, 98%yield, 84%ee) after post treatment.
Embodiment 6: preparation 5,6- dimethoxy -2- hydroxide radical-1-indenone -2- formic acid Buddha's warrior attendant ester
Weigh 0.037g (0.1mmol) 5,6- dimethoxy -1- indone -2- formic acid Buddha's warrior attendant ester (Ia-5), 0.0091g
5mL ethyl acetate is added in 20mL test tube in (0.01mmol, 10mol%) catalyst PTC-5, and solid is completely dissolved, and is denoted as a
Bottle；Another configuration 1%K2HPO4Solution is denoted as b bottles, and for entire reaction system controlled at 30 DEG C, a bottles of organic phases are pumped into speed from A
Rate is 2mL/min, and it is 2mL/min that aqueous slkali, which is pumped into rate from B, in b bottles, is passed through oxygen and helium mix gas (oxygen volume
Ratio 10%) flow velocity be 4mL/min, reaction pressure be 0bar (normal pressure), light source be 470nm LEDs, residence time 20min.It is former
Material conversion, organic phase completely obtain oxidation product IIa-5 (0.037g, 96%yield, 81%ee) after post treatment.
Embodiment 7: preparation 5- chlorine-2-hydroxyl -1- indone -2- formic acid Buddha's warrior attendant ester
Weigh the chloro- 1- indone -2- formic acid Buddha's warrior attendant ester (Ia-2) of 0.0344g (0.1mmol) 5-, 0.0077g (0.01mmol,
1mL toluene is added in 10mL test tube in 10mol%) catalyst PTC-6, and solid is completely dissolved, and is denoted as a bottles；Another configuration 1%
Cs2CO3Solution is denoted as b bottles, and for entire reaction system controlled at 20 DEG C, it is 1.5mL/ that a bottles of organic phases, which are pumped into rate from A,
In min, b bottles aqueous slkali from B be pumped into rate be 1.5mL/min, be passed through oxygen gas flow rate be 3mL/min, reaction pressure 1bar,
Light source is blue light, residence time 90min.Raw material converts completely, and organic phase obtains oxidation product IIa-1 after post treatment
(0.0336g, 93%yield, 90%ee).
Embodiment 8: preparation 5- chlorine-2-hydroxyl -1- indone -2- formic acid Buddha's warrior attendant ester technique amplifies 100 times of volumes
Weigh the chloro- 1- indone -2- formic acid Buddha's warrior attendant ester (Ia-2) of 3.44g (10mmol) 5-, 0.77g (1mmol, 10mol%)
100mL toluene is added in 200mL beaker in catalyst PTC-6, and solid is completely dissolved, and is denoted as a bottles；Another configuration 1%Cs2CO3It is molten
Liquid is denoted as b bottles, and for entire reaction system controlled at 20 DEG C, a bottles of organic phases are pumped into rate for 1.5mL/min, in b bottles from A
It is 1.5mL/min that aqueous slkali, which is pumped into rate from B, and being passed through oxygen gas flow rate is 3mL/min, and reaction pressure 1bar, light source is indigo plant
Light, residence time 90min.Raw material converts completely, organic phase obtain after post treatment oxidation product IIa-2 (3.355g, 93%
Yield, 90%ee).
Embodiment 9: preparation 5- chlorine-2-hydroxyl -1- indone -2- formic acid Buddha's warrior attendant ester technique amplifies 1000 times of volumes
Weigh the chloro- 1- indone -2- formic acid Buddha's warrior attendant ester (Ia-2) of 34.48g (100mmol) 5-, 7.7g (10mmol,
1L toluene is added in 2L beaker in 10mol%) catalyst PTC-6, and solid is completely dissolved, and is denoted as a bottles；Another configuration 1%Cs2CO3
Solution, is denoted as b bottles, and for entire reaction system controlled at 20 DEG C, it is 1.5mL/min that a bottles of organic phases, which are pumped into rate from A, and b bottles
It is 1.5mL/min that interior aqueous slkali, which is pumped into rate from B, and being passed through oxygen gas flow rate is 3mL/min, reaction pressure 1bar, and light source is
Blue light, residence time 90min.Raw material converts completely, organic phase obtain after post treatment oxidation product IIa-2 (33.58g, 93%
Yield, 90%ee).
Embodiment 10: preparation 2- hydroxide radical-1-indenone -2- methyl formate
0.019g (0.1mmol) 1- indone -2- methyl formate (Ia-6) is weighed, 0.043g (0.05mmol, 50mol%) is urged
1mL carbon tetrachloride is added in 10mL test tube in agent PTC-7, and solid is completely dissolved, and is denoted as a bottles；Another configuration 50%K2HPO4It is molten
Liquid, is denoted as b bottles, and for entire reaction system controlled at -15 DEG C, it is 0.3mL/min that a bottles of organic phases, which are pumped into rate from A, and b bottles
It is 0.3mL/min that interior aqueous slkali, which is pumped into rate from B, and being passed through oxygen (oxygen content 99%) flow velocity is 1mL/min, reaction pressure
For 3bar, light source is feux rouges, residence time 60min.Raw material converts completely, and organic phase obtains oxidation product IIa- after post treatment
6 (0.020g, 95%yield, 86%ee).
Embodiment 9: preparation 2- hydroxide radical-1-indenone -2- formic acid is to methyl phenyl ester
0.27g (1mmol) 1- indone -2- formic acid is weighed to methyl phenyl ester (Ia-7), 0.23g (0.3mmol, 30mol%)
1mL chloroform is added in 10mL test tube in catalyst PTC-8, and solid is completely dissolved, and is denoted as a bottles；Another configuration 10%K2HPO4It is molten
Liquid is denoted as b bottles, and for entire reaction system controlled at 0 DEG C, a bottles of organic phases are pumped into rate for 1.5mL/min, in b bottles from A
It is 1.5mL/min that aqueous slkali, which is pumped into rate from B, and being passed through oxygen (oxygen content 99.9%) flow velocity is 3mL/min, reaction pressure
For 0.5bar, light source is 600nm LEDs, residence time 150min.Raw material converts completely, and organic phase obtains oxygen after post treatment
Change product IIa-7 (0.26g, 91%yield, 85%ee).
Embodiment 10: preparation 2- hydroxyl -1-tetralone -2- formic acid Buddha's warrior attendant ester
Weigh 0.32g (1mmol) 1-tetralone -2- formic acid Buddha's warrior attendant ester (Ia-8), 0.07g (0.1mmol, 10mol%)
1mL methylene chloride is added in 10mL test tube in catalyst PTC-9, and solid is completely dissolved, and is denoted as a bottles；Another configuration 0.1%
K2HPO4Solution is denoted as b bottles, and for entire reaction system controlled at -5 DEG C, it is 1.5mL/ that a bottles of organic phases, which are pumped into rate from A,
It is 1.5mL/min that aqueous slkali, which is pumped into rate from B, in min, b bottles, is passed through oxygen and nitrogen mixed gas (oxygen content 50%)
Flow velocity is 3mL/min, and reaction pressure 2bar, light source is yellow light, residence time 200min.Raw material converts completely, organic phase warp
Later processing obtains oxidation product IIa-8 (0.30g, 89%yield, 82%ee).
Embodiment 11: preparation 2- hydroxyl 2- (4- methyl piperidine -1- carbonyl) -2,3- dihydro -1H- indone
Weigh 2.6g (10mmol) 2- (4- methyl piperidine -1- carbonyl) -2,3- dihydro -1H- indone (Ib-1), 0.009g
2mL chloroform is added in 10mL test tube in (0.01mmol, 0.1mol%) catalyst PTC-10, and solid is completely dissolved, and is denoted as a
Bottle；Another configuration 1%Na2CO3Solution is denoted as b bottles, and controlled at -10 DEG C, a bottles of organic phases are pumped into entire reaction system from A
Rate is 0.5mL/min, and it is 0.5mL/min that aqueous slkali, which is pumped into rate from B, in b bottles, is passed through oxygen (oxygen content 99.99%)
Flow velocity is 1.5mL/min, and reaction pressure 5bar, light source is 800nm LEDs, residence time 200min.Raw material converts completely,
Organic phase obtains oxidation product IIb-1 (2.6g, 96%yield, 84%ee) after post treatment.
Embodiment 12: preparation 2- hydroxy-N-methvl-N- phenyl -2,3- dihydro -1H- indone -2- formamide
0.027g (0.1mmol) N- Methyl-N-phenyl -2,3- dihydro -1H- indone -2- formamide (Ia-1) is weighed,
50mL petroleum ether is added in 100mL test tube in 0.028g (0.05mmol, 50mol%) catalyst PTC-11, and solid is completely molten
Solution, is denoted as a bottles；Another configuration 20%Na2CO3Solution, is denoted as b bottles, and entire reaction system is controlled at 5 DEG C, and a bottles of organic phases are from A
Being pumped into rate is 0.3mL/min, and it is 0.3mL/min that aqueous slkali, which is pumped into rate from B, in b bottles, and being passed through oxygen gas flow rate is 1mL/
Min, reaction pressure 6bar, light source are feux rouges, residence time 180min.Raw material converts completely, and organic phase obtains after post treatment
To oxidation product IIa-1 (0.026g, 93%yield, -78%ee).
Embodiment 1,3-7,10-12 are the quinine phase transfer catalyst for the C-2 ' modification having not been reported, and are demonstrated
It is not introduced under conditions of photosensitive group plus in photosensitizer or catalyst, catalyst itself has with chiral catalysis center and light
Difunctionalization at quick center, to greatly reduce the synthesis cost and reaction cost of catalyst.These embodiments simultaneously
Application of such catalyst in the photocatalysis asymmetric oxidation of catalysis beta-dicarbonyl compound is demonstrated, verifying it has well
Substrate application range.In embodiment 1-2 and 7-9, separately verified realized using microreactor amplify 10 in reaction volume~
It under the conditions of 1000 times of the case where, remains to be maintained under the identical residence time and obtains identical yield and enantioselectivity, be suitble to
" amplification " of reaction.
Embodiment described above only expresses embodiments of the present invention, and but it cannot be understood as to the invention patent
Range limitation, it is noted that for those skilled in the art, without departing from the inventive concept of the premise, also
Several modifications and improvements can be made, these are all belonged to the scope of protection of the present invention.
Claims (10)
1. a kind of new method for realizing visible light catalytic asymmetric oxidation using microreactor；It is characterized by: this method is logical
Micro passage reaction with gas-liquid mixed effect is crossed to realize, the reaction system in reactor be gas phase, water phase, organic phase three
Phase reaction system, under the conditions of radiation of visible light, using phase transfer catalyst derived from quinine, reaction temperature is -15~
30 DEG C, reaction time is 5~200min, it is seen that photoactivation oxygen realizes that beta-dicarbonyl compound is prepared hand by continuous oxidation
Property Alpha-hydroxy-beta-dicarbonyl compound；The a length of 300-800nm of visible light wave, reactor pressure 0 in the micro passage reaction
~6bar；
The organic phase is beta-dicarbonyl compound, phase transfer catalyst is molten with concentration by a certain percentage derived from quinine
Solution is in organic solvent, wherein and the molar ratio of phase transfer catalyst derived from beta-dicarbonyl compound and quinine is 0.1~
50mol%, the concentration of beta-dicarbonyl compound is 0.001~1mmol/ml in organic phase；
The water phase is the aqueous solution of inorganic base or inorganic salts, wherein alkali or salting liquid mass concentration are 0.01~50%；
The gas phase is the mixture of air, purity oxygen and the oxygen and inert gas prepared by a certain percentage, wherein gas phase
Middle oxygen proportion 1.0-99.99%.
2. the new photocatalysis asymmetric oxidation of one kind according to claim 1 prepares chiral alpha-hydroxy-beta-dicarbapentaborane chemical combination
The method of object, it is characterised in that: phase transfer catalyst PTC structure derived from the quinine is as follows:
Wherein, R1For hydroxyl；R2For fluorine, chlorine, bromine, iodine；R3For phenyl, naphthalene, m-trifluoromethylphenyl aryl substituent；R4For second
The aryl substituents such as alkenyl, ethyl, styryl, p-trifluoromethylstyrene base；R5、R6、R7、R8And R9For H, halogen, trifluoro
Methyl or methoxy, five is identical or different.
3. the new photocatalysis asymmetric oxidation of one kind according to claim 2 prepares chiral alpha-hydroxy-beta-dicarbapentaborane chemical combination
The method of object, it is characterised in that: in phase transfer catalyst PTC structure derived from the quinine, it is preferred that R2For bromine；R3
For phenyl, m-trifluoromethylphenyl；R4For vinyl；R5、R6、R9For H, R7、R8For bromine.
4. the new photocatalysis asymmetric oxidation of one kind according to claim 1 or 2 or 3 prepares-two carbonyl of chiral alpha-hydroxy-beta
The method of based compound, it is characterised in that: the beta-dicarbonyl compound includes Ia or Ib, photochemical catalytic oxidation beta-dicarbonyl
It includes following two that compound, which prepares the reaction for including in chiral alpha-hydroxy-beta-dicarbonyl compound method:
Wherein: R10For alkyl, naphthenic base, aromatic ring or benzyl, n is 1 or 2；R11-R13For hydrogen atom, halogen, alkyl, alkoxy,
Naphthenic base, three are identical or different；R14And R15For hydrogen atom, aromatic ring, alkyl, naphthenic base, the two is identical or different.
5. according to claim 1 or 2 or 3 a kind of new visible light catalytic asymmetric oxidation is realized using microreactor
Method, it is characterised in that: the flow velocity of the three-phase fluid is respectively as follows: the flow velocity 0.3-5mL/min of (1) organic phase；(2) water phase
Flow velocity 0.3-5mL/min；(3) the flow velocity 1-15mL/min of gas phase.
6. a kind of new method for realizing visible light catalytic asymmetric oxidation using microreactor according to claim 4,
It is characterized by: the flow velocity of the three-phase fluid is respectively as follows: the flow velocity 0.3-5mL/min of (1) organic phase；(2) stream of water phase
Fast 0.3-5mL/min；(3) the flow velocity 1-15mL/min of gas phase.
7. the new photocatalysis asymmetric oxidation of one kind described according to claim 1 or 2 or 3 or 6 prepares chiral alpha-hydroxy-beta-two
The method of carbonyls, it is characterised in that: the aqueous solution of the inorganic base or inorganic salts includes sodium carbonate, potassium carbonate, carbon
One or more kinds of mixing of sour caesium, sodium hydroxide, potassium hydroxide, dipotassium hydrogen phosphate, potassium dihydrogen phosphate etc..
8. the new photocatalysis asymmetric oxidation of one kind according to claim 4 prepares chiral alpha-hydroxy-beta-dicarbapentaborane chemical combination
The method of object, it is characterised in that: the aqueous solution of the inorganic base or inorganic salts includes sodium carbonate, potassium carbonate, cesium carbonate, hydrogen-oxygen
Change one or more kinds of mixing of sodium, potassium hydroxide, dipotassium hydrogen phosphate, potassium dihydrogen phosphate etc..
9. the new photocatalysis asymmetric oxidation of one kind described according to claim 1 or 2 or 3 or 6 or 8 prepares chiral Alpha-hydroxy-
The method of beta-dicarbonyl compound, it is characterised in that: the solvent includes aromatic hydrocarbons or alkanes, aromatic hydrocarbons include toluene,
Ortho-xylene, paraxylene, meta-xylene, mesitylene, p-chlorotoluene, ortho-chlorotolu'ene, alkanes include methylene chloride, chlorine
Imitative, carbon tetrachloride, petroleum ether, hexamethylene or ethyl acetate.
10. the new photocatalysis asymmetric oxidation of one kind according to claim 7 prepares chiral alpha-hydroxy-beta-dicarbapentaborane chemical combination
The method of object, it is characterised in that: the solvent includes aromatic hydrocarbons or alkanes, and aromatic hydrocarbons include toluene, ortho-xylene, to two
Toluene, meta-xylene, mesitylene, p-chlorotoluene, ortho-chlorotolu'ene, alkanes include methylene chloride, chloroform, carbon tetrachloride, stone
Oily ether, hexamethylene or ethyl acetate.
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