CN108745414B - Application of alcohol amine ionic liquid in catalysis of nucleophilic fluorination reaction in aqueous phase system - Google Patents
Application of alcohol amine ionic liquid in catalysis of nucleophilic fluorination reaction in aqueous phase system Download PDFInfo
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- B01J31/0279—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides comprising ionic liquids, as components in catalyst systems or catalysts per se, the ionic liquid compounds being used in the molten state at the respective reaction temperature containing nitrogen as cationic centre the cationic portion being acyclic or nitrogen being a substituent on a ring
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Abstract
The invention discloses application of an alcohol amine ionic liquid in catalysis of nucleophilic fluorination reaction in a water phase system, and belongs to the technical field of ionic liquid catalysis of nucleophilic fluorination reaction. The technical scheme provided by the invention has the key points that: halogenated compounds or sulfonyl substitutes are used as reaction substrates, potassium fluoride is used as a fluorine source, alcohol amine ionic liquid is used as a catalyst in a water phase system, heating reaction is carried out to prepare the target product, namely the fluorinated compounds, and the alcohol amine ionic liquid is recycled and reused. The alcamines ionic liquid is simple and convenient to prepare, low in price and easy to obtain; the reaction is carried out in an ionic liquid/water system, and an organic solvent is not required to be added, so that the method is environment-friendly; the reaction rate is high, and good yield can be achieved within 20 min; the potassium fluoride is used as a fluorine source, so that the cost is low; the catalyst can be repeatedly recycled.
Description
Technical Field
The invention belongs to the technical field of ionic liquid catalysis nucleophilic fluorination reaction, and particularly relates to application of alcohol amine ionic liquid in catalysis nucleophilic fluorination reaction in a water phase system.
Background
Fluorine chemistry is an important branch of organic chemistry, and organic fluorinated molecules have received much attention during the past decade. The combination of fluorine atoms can effectively improve the lipophilicity and metabolic stability of part of organic molecules (Shinde S, Patil S N, Ghatge A, et al]New Journal of Chemistry 2015,39(6):4368-4374.), to improve the potency and bioavailability of drug molecules (Watson D A, Su M, Teverovsky G, et al.Formation of arF from LPdAr (F): Catalytic conversion of aryl triflates to aryl fluorinates [ J]Science,2009,325(5948): 1661-1664.). Fluorine-containing drugs exhibit unique advantages in anticancer, antitumor, anti-inflammatory and other aspects (Dong Y, Wang Z, Li C. controlled radial contamination of poly (meth) acrylic acid in aqueous solution [ J)]Nature Communications,2017,8(1):277-280.), and, in addition, in the field of nuclear medicine, contains18Radiofluorides of F are also used as radiotracers in medical non-invasive imaging techniques, such as Positron Emission Tomography (PET) (Watson D A, SuM, Teverovsky G, et al. Formation of ArF from LPdAr (F): Catalytic conversion of aryl triflates to aryl fluorinates [ J]Science,2009,325(5948):1661-1664), and thus the fluorination reactions and fluorinated molecules are of great interest to pharmaceutical researchers. Nucleophilic substitution reactions using organic halides or sulfonic acid compounds with alkali metal fluorides are classical methods for introducing fluorine atoms into organic molecules, but such fluorination reactions using alkali metal fluorides as fluorine sources have many difficulties. First, since alkali metal fluorides such as cesium fluoride, potassium fluoride and the like can form strong hydrogen bonds with protic solvents, particularly water, the nucleophilicity of fluoride ions is reduced, and the occurrence of nucleophilic fluorination is suppressed (Lee JW, Oliveira M T, Jang H B, et al. hydrogen-bond promoted nuclear fluorination: concept, mechanism and applications in porous emission tomogry [ J]Chemical Society Reviews,2016,45(17): 4638-4650.); secondly, the higher lattice energy makes alkali metal fluorides almost freeSoluble in most aprotic solvents; the selectivity of the fluorination reaction is low due to the strong basicity of the fluoride ion (Lee E, KamLet A S, Powers DC, et al. A fluoride-derived electrophoretic late-stage fluoride reagent for PET imaging [ J]Science,2011,334(6056): 639-. Thus, aprotic solvents such as acetonitrile (Kim D W, Song C E, Chi D Y. New method of using fluorine in ionic liquid: halogenated enhanced reactivity of fluorine and enhanced selectivity [ J ] are generally used]Journal of the annular chemical facility, 2002,124(35):10278-10279.), or protic solvents that form weak hydrogen bonds with metal fluorides such as T-butanol, T-amyl alcohol (Kim D W, Jeong H J, Lim S T, et al]The Journal of organic chemistry,2008,73(3): 957-alcohol complexes modulators reactivity [ J ] and The like as reaction solvents, with The addition of additives to increase alkali metal fluoride solubility or to decrease fluoride ion basicity (Engle K M, Pfeifer L, Pidgeon G W, et al]Chemical Science,2015,6(9): 5293-. However, these catalytic systems have some drawbacks in some respects: the catalytic system is complex, toxic solvents and additives are required to be added, the catalyst is complex in structure and complex to synthesize, and the reaction time is long. Due to the fact that18The half-life of F is only 110min, so the fluorination speed directly determines whether a fluorination reaction can be applied to PET technology, and the faster reaction rate becomes the most demanded target.
In recent decades, with the introduction of green chemistry, ionic liquids have been vigorously developed as a new and green catalyst and solvent, and the research thereof has been more and more active, and the variety thereof has been increasing. Due to the rich variety and designability, people are often endowed with some special functions, and the method can be applied to many fields. Therefore, it has attracted a lot of attention in academia and industry. The ionic liquid has low volatility, designability, high thermal stability and chemical stabilityThe catalyst has the characteristics of high performance, strong catalytic activity, recyclability and the like, and has wide application prospect in the synthesis and catalysis industries. The ionic liquid also has certain application in catalyzing nucleophilic fluorination reaction. Such as [ BMIM ]][PF4](Kim D W,Song C E,Chi DY.New method of fluorination using potassium fluoride in ionic liquid:significantly enhanced reactivity of fluoride and improved selectivity[J].journal of the american chemical society,2002,124(35).)、[PMIM(SO3H)][OTf](Reddy A S,Laali K K.Mild and selectiveα-fluorination of carbonyl compounds(ketones,1,3-diketones,β-ketoesters,α-nitroketones,andβ-ketonitriles)with Selectfluor(F-TEDA-BF4)in imidazolium ILs[BMIM/PF6or BMIM/NTf2]with
IL[PMIM(SO3H)/OTf]as promoter[J].Tetrahedron Letters,2015,56(41):5495-5499.)、[MIM-tOH][OMs](Shinde S S,Patil S N,Ghatge A,et al.Nucleophilic fluorination using imidazolium based ionic liquid bearing tert-alcohol moiety[J].New Journal of Chemistry,2015,39(6):4368-4374.)、hexaEG-DtOHIM(Jadhav V H,Kim J G,Park S H,et al.Task-specific hexaethylene glycol bridged di-cationic ionic liquids as catalysts for nucleophilic fluorination using potassium fluoride[J]Chemical Engineering Journal 2017,308:664-668.) plasma liquids have all been used to catalyze nucleophilic fluorination, but there has been no article or related patent reporting the use of alcoholamine ionic liquids in nucleophilic fluorination reactions.
Disclosure of Invention
The invention solves the technical problem of providing a method for efficiently catalyzing nucleophilic fluorination reaction in an ionic liquid/water system by using cheap, easily obtained, convenient and efficient alcamines ionic liquid as a catalyst.
The invention adopts the following technical scheme for solving the technical problems, and the application of the alcohol amine ionic liquid in the catalysis of nucleophilic fluorination reaction in a water phase system is characterized in that: taking a halogenated compound or a sulfonyl substituent as a reaction substrate, taking potassium fluoride as a fluorine source, heating and reacting in a water phase system by taking an alcohol amine ionic liquid as a catalyst to prepare a target product, namely a fluorinated compound, and recycling the alcohol amine ionic liquid for repeated recycling;
the structural formula of the halogenated compound or the sulfonyl substituent is as follows:
the structural formula of the alcamines ionic liquid is as follows:
further preferably, the feeding molar ratio of the halogenated compound or the sulfonyl substituent to the potassium fluoride to the alcohol amine ionic liquid is 1:5: 4.
Further preferably, the heating reaction temperature is 140 ℃, and the reaction time is 10-20 min.
Further preferably, the application of the alcohol amine ionic liquid in catalyzing nucleophilic fluorination reaction in a water phase system is characterized by comprising the following specific steps: sequentially adding a reaction substrate, an alcohol amine ionic liquid, potassium fluoride and water into a pressure-resistant reaction vessel, sealing, dissolving the raw materials by preheating, putting the system into an oil bath after uniformly mixing, stirring for reaction at 140 ℃, adding cold water to quench the reaction after the reaction is finished, extracting the reaction mixture for three times by using ethyl acetate, combining organic phases, drying anhydrous sodium sulfate, carrying out spin drying on the organic phases to obtain a crude product, and carrying out silica gel column chromatographic separation on the crude product to obtain a pure target product, namely the fluoro compound; and removing water from the water phase after the extraction of the reaction mixture by reduced pressure rotary evaporation, dissolving the water phase with ethanol, filtering to remove residual inorganic salt, drying to obtain recovered alcohol amine ionic liquid, adding the reaction substrate, potassium fluoride and water again, and repeating the reaction process to realize the repeated recycling of the alcohol amine ionic liquid.
Compared with the prior art, the invention has the following advantages: (1) the alcamines ionic liquid is simple and convenient to prepare, low in price and easy to obtain; (2) the reaction is carried out in an ionic liquid/water system, and an organic solvent is not required to be added, so that the method is environment-friendly; (3) the reaction rate is high, and good yield can be achieved within 20 min; (4) the potassium fluoride is used as a fluorine source, so that the cost is low; (5) the catalyst can be repeatedly recycled.
Detailed Description
The present invention is described in further detail below with reference to examples, but it should not be construed that the scope of the above subject matter of the present invention is limited to the following examples, and that all the technologies realized based on the above subject matter of the present invention belong to the scope of the present invention.
Example 1
0.2mmol of 2- (3-bromopropoxy) -naphthalene, IL10.8mmol of alcamines ionic liquid, KF 1mmol and H are sequentially added into a 5mL thick-wall pressure-resistant bottle2O50 mu L, screwing a polytetrafluoroethylene cock, preheating by using a blower to dissolve the raw materials, and putting the system into a 140 ℃ oil bath to perform heating reaction for 20min after the system is uniformly mixed. After the reaction is stopped, adding 1mL of cold water into a pressure-resistant bottle to quench the reaction, extracting with 2mL of ethyl acetate for three times, combining organic phases, drying by anhydrous sodium sulfate, spin-drying the organic phases to obtain a crude product, and performing nuclear magnetic hydrogen spectrum analysis to obtain a target product with the yield of 63%.
Example 2
0.2mmol of 2- (3-bromopropoxy) -naphthalene, IL20.8mmol of alcamines ionic liquid, KF 1mmol and H are sequentially added into a 5mL thick-wall pressure-resistant bottle2O50 mu L, screwing a polytetrafluoroethylene cock, preheating by using a blower to dissolve the raw materials, and putting the system into a 140 ℃ oil bath to perform heating reaction for 20min after the system is uniformly mixed. After the reaction was stopped, 1mL of cold water was added to the pressure bottle to quench the reaction, and 2mL of the solution was usedExtracting with ethyl acetate for three times, combining organic phases, drying with anhydrous sodium sulfate, carrying out spin drying on the organic phases to obtain a crude product, and carrying out nuclear magnetic hydrogen spectrum analysis to obtain a target product with the yield of 77%.
Example 3
0.2mmol of 2- (3-bromopropoxy) -naphthalene, IL30.8mmol of alcamines ionic liquid, KF 1mmol and H are sequentially added into a 5mL thick-wall pressure-resistant bottle2O50 mu L, screwing a polytetrafluoroethylene cock, preheating by using a blower to dissolve the raw materials, and putting the system into a 140 ℃ oil bath to perform heating reaction for 20min after the system is uniformly mixed. After the reaction is stopped, adding 1mL of cold water into a pressure-resistant bottle to quench the reaction, extracting with 2mL of ethyl acetate for three times, combining organic phases, drying by anhydrous sodium sulfate, spin-drying the organic phases to obtain a crude product, and performing nuclear magnetic hydrogen spectrum analysis to obtain the target product with the yield of 60%.
Example 4
0.2mmol of 2- (3-bromopropoxy) -naphthalene, IL40.8mmol of alcamines ionic liquid, KF 1mmol and H are sequentially added into a 5mL thick-wall pressure-resistant bottle2O50 mu L, screwing a polytetrafluoroethylene cock, preheating by using a blower to dissolve the raw materials, and putting the system into a 140 ℃ oil bath to perform heating reaction for 20min after the system is uniformly mixed. After the reaction is stopped, adding 1mL of cold water into a pressure-resistant bottle to quench the reaction, extracting with 2mL of ethyl acetate for three times, combining organic phases, drying by anhydrous sodium sulfate, spin-drying the organic phases to obtain a crude product, and analyzing by nuclear magnetic hydrogen spectrum to obtain the target product with the yield of 61%.
Example 5
0.2mmol of 2- (3-bromopropoxy) -naphthalene, IL50.8mmol of alcamines ionic liquid, KF 1mmol and H are sequentially added into a 5mL thick-wall pressure-resistant bottle2O50 mu L, screwing a polytetrafluoroethylene cock, preheating by using a blower to dissolve the raw materials, and putting the system into a 140 ℃ oil bath to perform heating reaction for 20min after the system is uniformly mixed. After the reaction is stopped, adding 1mL of cold water into a pressure-resistant bottle to quench the reaction, extracting with 2mL of ethyl acetate for three times, combining organic phases, drying by anhydrous sodium sulfate, spin-drying the organic phases to obtain a crude product, and performing nuclear magnetic hydrogen spectrum analysis to obtain the target product with the yield of 60%.
Example 6
Sequentially adding 0.2mmol of 2- (3-bromopropoxy) -naphthalene and alcamines into a 5mL thick-wall pressure-resistant bottleThe sub-liquid IL60.8mmol, KF 1mmol and H2O50 mu L, screwing a polytetrafluoroethylene cock, preheating by using a blower to dissolve the raw materials, and putting the system into a 140 ℃ oil bath to perform heating reaction for 20min after the system is uniformly mixed. After the reaction is stopped, adding 1mL of cold water into a pressure-resistant bottle to quench the reaction, extracting with 2mL of ethyl acetate for three times, combining organic phases, drying by anhydrous sodium sulfate, spin-drying the organic phases to obtain a crude product, and performing nuclear magnetic hydrogen spectrum analysis to obtain the target product with the yield of 60%.
Example 7
0.2mmol of 2- (3-bromopropoxy) -naphthalene, IL30.8mmol of alcamines ionic liquid, KF 1mmol and H are sequentially added into a 5mL thick-wall pressure-resistant bottle2O50 mu L, screwing a polytetrafluoroethylene cock, preheating by using a blower to dissolve the raw materials, and putting the system into a 140 ℃ oil bath to perform heating reaction for 20min after the system is uniformly mixed. After the reaction is stopped, adding 1mL of cold water into a pressure-resistant bottle to quench the reaction, extracting with 2mL of ethyl acetate for three times, combining organic phases, drying by anhydrous sodium sulfate, spin-drying the organic phases to obtain a crude product, and analyzing by nuclear magnetic hydrogen spectrometry to obtain the target product with the yield of 62%.
Example 8
0.2mmol of 2- (3-bromopropoxy) -naphthalene, IL30.8mmol of alcamines ionic liquid, KF 1mmol and H are sequentially added into a 5mL thick-wall pressure-resistant bottle2O50 mu L, screwing a polytetrafluoroethylene cock, preheating by using a blower to dissolve the raw materials, and putting the system into a 140 ℃ oil bath to perform heating reaction for 20min after the system is uniformly mixed. After the reaction is stopped, adding 1mL of cold water into a pressure-resistant bottle to quench the reaction, extracting with 2mL of ethyl acetate for three times, combining organic phases, drying by anhydrous sodium sulfate, spin-drying the organic phases to obtain a crude product, and analyzing by nuclear magnetic hydrogen spectrum to obtain the target product with the yield of 61%.
Example 9
Adding 0.2mmol of 2- (3-iodopropoxy) -naphthalene and C into a 5mL thick-wall pressure-resistant bottle in sequence80.8mmol of DMEABR ionic liquid, 1mmol of KF and H2O50 mu L, screwing a polytetrafluoroethylene cock, preheating by using a blower to dissolve the raw materials, and putting the system into a 140 ℃ oil bath to perform heating reaction for 20min after the system is uniformly mixed. After the reaction is stopped, 1mL of cold water is added into a pressure-resistant bottle to quench the reaction, 2mL of ethyl acetate is used for extraction for three times, and organic phases are combined and anhydrousDrying with sodium sulfate, spin-drying the organic phase to obtain a crude product, and analyzing by nuclear magnetic hydrogen spectrum to obtain the target product with the yield of 73%.
Example 10
Adding 0.2mmol of 1- (3-bromopropoxy) -naphthalene and C into a 5mL thick-wall pressure-resistant bottle in sequence80.8mmol of DMEABR ionic liquid, 1mmol of KF and H2O50 mu L, screwing a polytetrafluoroethylene cock, preheating by using a blower to dissolve the raw materials, and putting the system into a 140 ℃ oil bath to perform heating reaction for 20min after the system is uniformly mixed. After the reaction is stopped, adding 1mL of cold water into a pressure-resistant bottle to quench the reaction, extracting with 2mL of ethyl acetate for three times, combining organic phases, drying by anhydrous sodium sulfate, spin-drying the organic phases to obtain a crude product, and analyzing by nuclear magnetic hydrogen spectrum to obtain the target product with the yield of 81%.
Example 11
Adding 0.2mmol of 2- (6-bromopropoxy) -naphthalene and C into a 5mL thick-wall pressure-resistant bottle in sequence80.8mmol of DMEABR ionic liquid, 1mmol of KF and H2O50 mu L, screwing a polytetrafluoroethylene cock, preheating by using a blower to dissolve the raw materials, and putting the system into a 140 ℃ oil bath to perform heating reaction for 20min after the system is uniformly mixed. After the reaction is stopped, adding 1mL of cold water into a pressure-resistant bottle to quench the reaction, extracting with 2mL of ethyl acetate for three times, combining organic phases, drying by anhydrous sodium sulfate, spin-drying the organic phases to obtain a crude product, and analyzing by nuclear magnetic hydrogen spectrum to obtain the target product with the yield of 80%.
Example 12
Adding 0.2mmol of 2- (3-p-toluenesulfonylpropoxy) -naphthalene and C into a 5mL thick-wall pressure-resistant bottle in sequence80.8mmol of DMEABR ionic liquid, 1mmol of KF and H2O50 mu L, screwing a polytetrafluoroethylene cock, preheating by using a blower to dissolve the raw materials, and putting the system into a 140 ℃ oil bath to perform heating reaction for 20min after the system is uniformly mixed. After the reaction is stopped, adding 1mL of cold water into a pressure-resistant bottle to quench the reaction, extracting with 2mL of ethyl acetate for three times, combining organic phases, drying by anhydrous sodium sulfate, spin-drying the organic phases to obtain a crude product, and performing nuclear magnetic hydrogen spectrum analysis to obtain a target product with the yield of 70%.
Example 13
Adding 0.2mmol of 2- (3-methylsulfonylpropoxy) -naphthalene and C into a 5mL thick-wall pressure-resistant bottle in sequence8DMEA0.8mmol of Br ionic liquid, 1mmol of KF and H2O50 mu L, screwing a polytetrafluoroethylene cock, preheating by using a blower to dissolve the raw materials, and putting the system into a 140 ℃ oil bath to perform heating reaction for 20min after the system is uniformly mixed. After the reaction is stopped, adding 1mL of cold water into a pressure-resistant bottle to quench the reaction, extracting with 2mL of EA for three times, combining organic phases, drying with anhydrous sodium sulfate, spin-drying the organic phases to obtain a crude product, and performing nuclear magnetic hydrogen spectrum analysis to obtain a target product with the yield of 71%.
Example 14
Sequentially adding 0.2mmol of 2-bromoacetophenone and C into a 5mL thick-wall pressure-resistant bottle80.8mmol of DMEABR ionic liquid, 1mmol of KF and H2O50 mu L, screwing a polytetrafluoroethylene cock, preheating by using a blower to dissolve the raw materials, and putting the system into a 140 ℃ oil bath for heating reaction for 10min after the system is uniformly mixed. After the reaction is stopped, adding 1mL of cold water into a pressure-resistant bottle to quench the reaction, extracting with 2mL of ethyl acetate for three times, combining organic phases, drying by anhydrous sodium sulfate, spin-drying the organic phases to obtain a crude product, and performing nuclear magnetic hydrogen spectrum analysis to obtain the target product with the yield of 95%.
Example 15
Sequentially adding 0.2mmol of isopropyl-2-bromoacetophenone and C into a 5mL thick-wall pressure-resistant bottle80.8mmol of DMEABR ionic liquid, 1mmol of KF and H2O50 mu L, screwing a polytetrafluoroethylene cock, preheating by using a blower to dissolve the raw materials, and putting the system into a 140 ℃ oil bath to perform heating reaction for 20min after the system is uniformly mixed. After the reaction is stopped, adding 1mL of cold water into a pressure-resistant bottle to quench the reaction, extracting with 2mL of ethyl acetate for three times, combining organic phases, drying by anhydrous sodium sulfate, spin-drying the organic phases to obtain a crude product, and performing nuclear magnetic hydrogen spectrum analysis to obtain the target product with the yield of 91%.
Example 16
Sequentially adding 0.2mmol of bromoacetophenone and C into a 5mL thick-wall pressure-resistant bottle80.8mmol of DMEABR ionic liquid, 1mmol of KF and H2O50 mu L, screwing a polytetrafluoroethylene cock, preheating by using a blower to dissolve the raw materials, and putting the system into a 140 ℃ oil bath to perform heating reaction for 20min after the system is uniformly mixed. After the reaction was stopped, 1mL of cold water was added to the pressure bottle to quench the reaction, extracted three times with 2mL of ethyl acetate, and the organic phases were combined and eliminatedDrying with sodium sulfate, spin-drying the organic phase to obtain a crude product, and analyzing by nuclear magnetic hydrogen spectrum to obtain the target product with the yield of 98%.
Example 17
Sequentially adding 0.2mmol of p-methoxy-2-bromoacetophenone and C into a 5mL thick-wall pressure-resistant bottle80.8mmol of DMEABR ionic liquid, 1mmol of KF and H2O50 mu L, screwing a polytetrafluoroethylene cock, preheating by using a blower to dissolve the raw materials, and putting the system into a 140 ℃ oil bath for heating reaction for 10min after the system is uniformly mixed. After the reaction is stopped, adding 1mL of cold water into a pressure-resistant bottle to quench the reaction, extracting with 2mL of ethyl acetate for three times, combining organic phases, drying by anhydrous sodium sulfate, spin-drying the organic phases to obtain a crude product, and analyzing by nuclear magnetic hydrogen spectrum to obtain the target product with the yield of 84%.
Example 18
Recycling situation
Adding 0.2mmol of 2- (3-bromopropoxy) -naphthalene and C into a 5mL thick-wall pressure-resistant bottle in sequence80.8mmol of DMEABR ionic liquid, 1mmol of KF and H2O50 mu L, screwing a polytetrafluoroethylene cock, preheating by using a blower to dissolve the raw materials, and putting the system into a 140 ℃ oil bath to perform heating reaction for 20min after the system is uniformly mixed. After the reaction is stopped, adding 1mL of cold water into a pressure-resistant bottle to quench the reaction, extracting with 2mL of ethyl acetate for three times, combining organic phases, drying by anhydrous sodium sulfate, spin-drying the organic phases to obtain a crude product, and analyzing by nuclear magnetic hydrogen spectrum to obtain the target product with the yield of 77%.
The reaction was carried out using the probe of example 2 as catalyst C8Activity repeatability test of DMEABr Ionic liquids, C8The DMEABR ionic liquid is repeatedly used for 5 times, and the yield of the target product is shown in Table 1.
TABLE 1C8The ionic liquid of DMEABR is recycled
As can be seen from table 1: c8After the DMEABR ionic liquid is recycled for 5 times in the process of recycling and catalyzing nucleophilic fluorination reaction, the yield is still high, which shows that C8DMEABR ionic liquid inThe catalyst can be repeatedly recycled in the process of catalyzing nucleophilic fluorination.
The foregoing embodiments illustrate the principles, principal features and advantages of the invention, and it will be understood by those skilled in the art that the invention is not limited to the foregoing embodiments, which are merely illustrative of the principles of the invention, and that various changes and modifications may be made therein without departing from the scope of the principles of the invention.
Claims (4)
1. The application of the alcohol amine ionic liquid in the catalysis of nucleophilic fluorination reaction in a water phase system is characterized in that: taking a halogenated compound or a sulfonyl substituent as a reaction substrate, taking potassium fluoride as a fluorine source, heating and reacting in a water phase system by taking an alcohol amine ionic liquid as a catalyst to prepare a target product, namely a fluorinated compound, and recycling the alcohol amine ionic liquid for repeated recycling;
the structural formula of the halogenated compound or the sulfonyl substituent is as follows:
the structural formula of the alcamines ionic liquid is as follows:
2. the application of the alcohol amine ionic liquid in catalyzing nucleophilic fluoro reaction in an aqueous phase system according to claim 1, wherein: the feeding molar ratio of the halogenated compound or the sulfonyl substituent to the potassium fluoride to the alcohol amine ionic liquid is 1:5: 4.
3. The application of the alcohol amine ionic liquid in catalyzing nucleophilic fluoro reaction in an aqueous phase system according to claim 1, wherein: the heating reaction temperature is 140 ℃, and the reaction time is 10-20 min.
4. The application of the alcohol amine ionic liquid in catalyzing nucleophilic fluorination reaction in an aqueous phase system according to claim 1 is characterized by comprising the following specific steps: sequentially adding a reaction substrate, an alcohol amine ionic liquid, potassium fluoride and water into a pressure-resistant reaction vessel, sealing, dissolving the raw materials by preheating, putting the system into an oil bath after uniformly mixing, stirring for reaction at 140 ℃, adding cold water to quench the reaction after the reaction is finished, extracting the reaction mixture for three times by using ethyl acetate, combining organic phases, drying anhydrous sodium sulfate, carrying out spin drying on the organic phases to obtain a crude product, and carrying out silica gel column chromatographic separation on the crude product to obtain a pure target product, namely the fluoro compound; and removing water from the water phase after the extraction of the reaction mixture by reduced pressure rotary evaporation, dissolving the water phase with ethanol, filtering to remove residual inorganic salt, drying to obtain recovered alcohol amine ionic liquid, adding the reaction substrate, potassium fluoride and water again, and repeating the reaction process to realize the repeated recycling of the alcohol amine ionic liquid.
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| CN106220509A (en) * | 2016-07-25 | 2016-12-14 | 河南师范大学 | The method of alcamines ionic liquid-catalyzed synthesis xanthenedione compounds p-Coumaric acid |
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| CN108067301A (en) * | 2016-11-15 | 2018-05-25 | 中国科学院大连化学物理研究所 | A kind of quaternary ammonium salt ionic liquid polyalcohol catalyst is in CO2It is applied in cycloaddition reaction |
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