CN112898326A - Preparation method and application of organic boron compound, and preparation method and application of beta-hydroxy compound - Google Patents
Preparation method and application of organic boron compound, and preparation method and application of beta-hydroxy compound Download PDFInfo
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- CN112898326A CN112898326A CN202110046750.2A CN202110046750A CN112898326A CN 112898326 A CN112898326 A CN 112898326A CN 202110046750 A CN202110046750 A CN 202110046750A CN 112898326 A CN112898326 A CN 112898326A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
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- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/31—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by introduction of functional groups containing oxygen only in singly bound form
Abstract
The invention discloses a preparation method and application of an organic boron compound, and a preparation method and application of a beta-hydroxyl compound, wherein the preparation method of the organic boron compound comprises the following steps: stirring a compound I, pinacol diboron, a catalyst and water at room temperature for reaction, and separating and purifying a reaction product after the reaction is finished to obtain an organic boron compound; the structural formula of the compound I is shown in a structural formula (I), the structural general formula of the organic boron compound is shown in a structural formula (II), and the catalyst is a chitosan/polyvinyl alcohol immobilized nano copper composite membrane. The preparation method provided by the invention is simple and easy to operate, has low catalyst consumption, is easy to separate after the reaction is finished, has no metal residue, and is suitable for large-scale production.
Description
Technical Field
The invention relates to the technical field of organic synthesis, in particular to a preparation method and application of an organic boron compound and a preparation method and application of a beta-hydroxy compound.
Background
The organic boron compound is an important intermediate and is widely applied to synthesis of natural products and drug molecules, because a C-B bond can be simply and conveniently converted into a C-O, C-N bond and a C-C bond, wherein the Morita-Baylis-Hillman organic boron compound simultaneously has an allyl group and an alpha, beta-unsaturated carbonyl structure, and is a convenient and efficient intermediate compound for synthesizing multi-substituted functionalized drug molecules.
Disclosure of Invention
The invention mainly aims to provide a preparation method and application of an organic boron compound, and a preparation method and application of a beta-hydroxy compound, and aims to solve the problems that a catalyst is difficult to remove after reaction is finished and the residual quantity is high in the existing preparation method of the organic boron compound.
To achieve the above object, the present invention provides a process for producing an organoboron compound, comprising the steps of:
stirring a compound I, pinacol diboron, a catalyst and water at room temperature for reaction, and separating and purifying a reaction product after the reaction is finished to obtain an organic boron compound;
the structural formula of the compound I is shown as the following structural formula (I), the structural general formula of the organic boron compound is shown as the following structural formula (II), and the catalyst is a chitosan/polyvinyl alcohol immobilized nano copper composite membrane;
in the structural formula (I) and the structural formula (II), R groups are phenyl ketone groups, p-halogenophenyl ketone groups, p-methyl phenyl ketone groups, p-methoxy phenyl ketone groups, acyl groups, ester groups or cyano groups.
Optionally, the p-halophenonyl group is p-fluorophenonyl or p-chlorophenoxyl; alternatively, the first and second electrodes may be,
the acyl group is acetyl; alternatively, the first and second electrodes may be,
the ester group is a methyl ester group or an ethyl ester group.
Optionally, the ratio of the amount of the substance of the compound I to the volume of the water is 1-2 mmol: 10 mL; and/or the presence of a gas in the gas,
the mass ratio of the compound I to the pinacol ester diborate is (1.2-2.0): 1; and/or the presence of a gas in the gas,
the mass ratio of the substance of the compound I to the catalyst is 1-2 mmol: 25 mg; and/or the presence of a gas in the gas,
the reaction temperature of the stirring reaction is 20-25 ℃, and the reaction time is 10-14 h.
Optionally, the step of separating and purifying the reaction product after the reaction is finished to obtain the organoboron compound comprises:
and after the reaction is finished, filtering the reaction system to remove the catalyst, washing the filtrate by adopting tetrahydrofuran, evaporating and concentrating, carrying out column chromatography on the concentrated residue by using a mixed solvent of ethyl acetate and petroleum ether, and purifying to obtain the organic boron compound.
The invention also provides a pharmaceutical formulation comprising an organoboron compound prepared by the process for preparing an organoboron compound as described above.
The invention also provides a preparation method of the beta-hydroxy compound, which comprises the following steps:
carrying out a first stirring reaction on the compound I, the diboron pinacol ester, a catalyst and water at room temperature, and removing the catalyst after the reaction is finished to obtain an intermediate system with an organic boron compound;
adding sodium perborate tetrahydrate into the intermediate system, carrying out a second stirring reaction at room temperature, and separating and purifying a reaction product after the reaction is finished to obtain a beta-hydroxy compound;
the structural formula of the compound I is shown as the following structural formula (I), the structural general formula of the organic boron compound is shown as the following structural formula (II), the structural general formula of the beta-hydroxyl compound is shown as the following structural formula (III), and the catalyst is a chitosan/polyvinyl alcohol immobilized nano copper composite membrane;
in the structural formula (I), the structural formula (II) and the structural formula (III), R groups are phenyl ketone groups, p-halogenophenyl ketone groups, p-methylbenzyl ketone groups, p-methoxybenzyl ketone groups, acyl groups, ester groups or cyano groups.
Optionally, the p-halophenonyl group is p-fluorophenonyl or p-chlorophenoxyl; and/or the presence of a gas in the gas,
the acyl group is acetyl; and/or the presence of a gas in the gas,
the ester group is a methyl ester group or an ethyl ester group.
Optionally, the ratio of the amount of the substance of the compound I to the volume of the water is 1-2 mmol: 10 mL; and/or the presence of a gas in the gas,
the mass ratio of the compound I to the pinacol ester diborate is (1.2-2.0): 1; and/or the presence of a gas in the gas,
the mass ratio of the substance of the compound I to the catalyst is 1-2 mmol: 25 mg; and/or the presence of a gas in the gas,
the mass ratio of the compound I to the sodium perborate tetrahydrate is 1: 4.
Optionally, the reaction temperature of the first stirring reaction is 20-25 ℃, and the reaction time is 10-14 h; and/or the presence of a gas in the gas,
the reaction temperature of the second stirring reaction is 20-25 ℃, and the reaction time is 3-5 h.
The invention also provides a pharmaceutical preparation which comprises the beta-hydroxy compound, and the beta-hydroxy compound is prepared by the preparation method of the beta-hydroxy compound.
According to the technical scheme provided by the invention, the chitosan/polyvinyl alcohol immobilized nano copper composite membrane is used as a catalyst, the pinacol biborate ester is used as a reaction reagent, and the reaction in water can reach high reaction activity, so that the boron addition of a substrate is realized under mild conditions, and the Morita-Baylis-Hillman organic boron compound containing different substituents is prepared.
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. The examples, in which specific conditions are not specified, were conducted under conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used are not indicated by the manufacturer, and are all conventional products available commercially. In addition, the meaning of "and/or" appearing throughout includes three juxtapositions, exemplified by "A and/or B" including either A or B or both A and B. In addition, technical solutions between various embodiments may be combined with each other, but must be realized by a person skilled in the art, and when the technical solutions are contradictory or cannot be realized, such a combination should not be considered to exist, and is not within the protection scope of the present invention. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
The invention provides a preparation method of an organic boron compound, which comprises the following steps: stirring a compound I, pinacol diboron, a catalyst and water at room temperature for reaction, and separating and purifying a reaction product after the reaction is finished to obtain an organic boron compound; the structural formula of the compound I is shown as the following structural formula (I), the structural general formula of the organic boron compound is shown as the following structural formula (II), and the catalyst is a chitosan/polyvinyl alcohol immobilized nano copper composite membrane;
in the structural formula (I) and the structural formula (II), R groups are phenyl ketone groups, p-halogenophenyl ketone groups, p-methyl phenyl ketone groups, p-methoxy phenyl ketone groups, acyl groups, ester groups or cyano groups.
Chitosan is a kind of natural alkaline polysaccharide, which has biological functionality, biocompatibility, low toxicity, biodegradability and almost no anaphylactic effect, has the characteristics of large distribution amount, rich resources, simplicity and easy obtainment in China, has good chelating capacity for metals, and can be used as a catalyst and an initiator for reactions such as hydrogenation, oxidative coupling, ring-opening polymerization, alkene monomer polymerization, esterification, etherification and the like. The inventor researches and discovers that the chitosan/polyvinyl alcohol immobilized nano copper composite membrane has a good catalytic effect when being used as a catalyst for catalytic reaction, and further researches and discovers that the catalyst has a good catalytic effect when being used for synthesizing a Morita-Baylis-Hillman organic boron compound, avoids using strong base with high pollution, greatly reduces the using amount of the catalyst, has no metal residue, can use pure water as a reaction solvent, and is more environment-friendly in reaction.
According to the technical scheme provided by the invention, the chitosan/polyvinyl alcohol immobilized nano copper composite membrane is used as a catalyst, the pinacol biborate ester is used as a reaction reagent, and the reaction in water can reach high reaction activity, so that the boron addition of a substrate is realized under mild conditions, and the Morita-Baylis-Hillman organic boron compound containing different substituents is prepared.
In particular toThe method for producing the organoboron compound can be carried out in the following manner: adding a chitosan/polyvinyl alcohol immobilized nano-copper composite membrane catalyst (CP @ Cu NPs) into a reaction vessel, then adding water, stirring and dispersing for 1-2 h at room temperature, and then continuously and sequentially adding the compound I and the diboronic acid pinacol ester (B)2(pin)2) Stirring and reacting at room temperature, and in the reaction process, under the catalysis of a chitosan/polyvinyl alcohol immobilized nano copper composite membrane (CP @ Cu NPs), a substrate (namely a compound I) and pinacol diboron (B)2(pin)2) Adsorbing the catalyst on the surface of the catalyst to be close to each other, forming a complex metal complex by copper and diboronic acid pinacol ester, carrying out addition on a substrate, transferring a boron group connected with the copper to the substrate in a six-membered ring transition state, and selectively finishing the direct boron addition process to prepare the organic boron compound, wherein the chemical reaction equation is as follows:
in the structural formula (I) and the structural formula (II), the R group can be any one of a phenyl ketone group, a p-halophenyl ketone group, a p-methylphenyl ketone group, a p-methoxy phenyl ketone group, an acyl group, an ester group and a cyano group, and during actual preparation, reaction raw materials with different groups are correspondingly selected according to different product requirements. Further, when the R group is a p-halophenonyl group, it is more preferably a p-fluorophenonyl group or a p-chlorophenoxy group; alternatively, when the R group is acyl, acetyl is more preferred; alternatively, when the R group is an ester group, it is more preferably a methyl ester group or an ethyl ester group.
Further, the addition ratio relationship of each raw material in the reaction is preferably as follows: the ratio of the amount of the substance of the compound I to the volume of the water is 1-2 mmol: 10mL, more preferably 1 mmol: 10 mL; and/or the mass ratio of the compound I to the pinacol ester diborate is (1.2-2.0): 1, more preferably 1.2: 1; and/or the mass ratio of the substance of the compound I to the catalyst is 1-2 mmol: 25mg, more preferably 1 mmol: 25 mg. Under the condition of the addition proportion, the compound I and the diboron pinacol ester can fully react under the action of a catalyst to generate an organic boron compound, and the reaction rate is high and the efficiency is high.
The stirring reaction can be carried out at room temperature without external heating, which is beneficial to reducing the process cost. Further, in order to ensure the smooth proceeding of the reaction, the stirring reaction is preferably carried out at the room temperature of 20-25 ℃, and the reaction time is 10-14 h, so that the influence of over-high or over-low room temperature on the reaction efficiency is avoided.
In the preparation method of the organic boron compound, the chitosan/polyvinyl alcohol immobilized nano copper composite membrane is used as the catalyst, the dosage is small, the catalytic efficiency is high, the catalyst is easy to separate after the reaction is finished, and the catalyst can be thoroughly removed from the reaction system by adopting a conventional mode of solid-liquid separation such as filtration, centrifugation and the like, and has no metal residue. Specifically, in the specific embodiment provided by the present invention, the step of separating and purifying the reaction product after the reaction is finished to obtain the organoboron compound includes:
after the reaction is finished, filtering the reaction system to remove the catalyst, washing the filtrate by adopting tetrahydrofuran, performing rotary evaporation concentration, performing column chromatography on the concentrated residue by using mixed solvents of ethyl acetate and petroleum ether in different proportions, and separating and purifying to obtain an organic boron compound; the proportion of the mixed solvent of the ethyl acetate and the petroleum ether is selected according to different polarities of the product, and silica gel is used as a stationary phase for column chromatography.
The preparation method of the organic boron compound provided by the invention has the advantages of mild reaction conditions, simple process flow and small catalyst consumption, the catalyst can be separated and recovered through simple filtering operation after the reaction is finished, the effective separation of the catalyst can be realized, no metal residue exists, the chitosan/polyvinyl alcohol immobilized nano copper composite membrane catalyst can be reused after being recovered, and the catalytic reaction is carried out without activity loss. After the reaction is finished, the chitosan/polyvinyl alcohol immobilized nano-copper composite membrane catalyst is recovered by filtration and directly used for the next round of reaction, the yield of the target product obtained by repeating the step five times is respectively 99%, 98%, 96% and 99%, and the catalyst activity is proved to have almost no loss and can be recycled.
The organic boron compound prepared by the method provided by the invention has wide practical application, such as an initiator of polymerization reaction, an antioxidant, a bactericide, a neutron capture agent, a medicament for treating brain tumor and resisting cancer, and the like. Based on the above, the present invention further provides a pharmaceutical preparation, which comprises the organoboron compound, wherein the organoboron compound is prepared by the preparation method of the organoboron compound as described above, the pharmaceutical preparation includes but is not limited to a pharmaceutical preparation for treating brain tumor and/or resisting cancer, and in addition to taking the organoboron compound as an active ingredient, the pharmaceutical preparation can be added with auxiliary ingredients such as a carrier, which are not described herein again.
The conversion of the organoboron compound to the beta-hydroxy compound is an important application field, because the beta-hydroxy structure widely exists in a natural product structure, if a 'one-pot method' strategy can be adopted, the boron addition of a substrate is firstly realized, and then the substrate can be continuously converted into the beta-hydroxy compound without separation, so that the synthetic steps of the natural product are simplified, and the method has an important application value. Therefore, the invention further provides a preparation method of the beta-hydroxy compound, which comprises the following steps:
step S10, carrying out a first stirring reaction on the compound I, the pinacol diboron, the catalyst and water at room temperature, and removing the catalyst after the reaction is finished to obtain an intermediate system with the organic boron compound;
step S20, adding sodium perborate tetrahydrate into the intermediate system, carrying out a second stirring reaction at room temperature, and separating and purifying a reaction product after the reaction is finished to obtain a beta-hydroxy compound;
the structural formula of the compound I is shown as the following structural formula (I), the structural general formula of the organic boron compound is shown as the following structural formula (II), the structural general formula of the beta-hydroxyl compound is shown as the following structural formula (III), and the catalyst is a chitosan/polyvinyl alcohol immobilized nano copper composite membrane;
in the structural formula (I), the structural formula (II) and the structural formula (III), R groups are phenyl ketone groups, p-halogenophenyl ketone groups, p-methylbenzyl ketone groups, p-methoxybenzyl ketone groups, acyl groups, ester groups or cyano groups.
In the technical scheme provided by the invention, a chitosan/polyvinyl alcohol immobilized nano-copper composite membrane (CP @ Cu NPs) is used as a catalyst, and pinacol ester diboron (B)2(pin)2) The method is characterized in that a reaction reagent, water as a solvent and sodium perborate tetrahydrate as an oxidant are adopted, 1, 4-selective boron addition reaction is carried out on substrates containing different substituents respectively to prepare an organic boron compound, then the functional group conversion is directly realized through continuous oxidation reaction, and a functional molecular beta-hydroxy compound is prepared by a one-pot method, so that the preparation method of the beta-hydroxy compound is simplified. Specifically, in the specific examples provided herein, the preparation method of the β -hydroxy compound may be implemented by:
firstly, adding a chitosan/polyvinyl alcohol immobilized nano-copper composite membrane catalyst into a reaction vessel, then adding water, stirring and dispersing for 1-2 h at room temperature, then continuously and sequentially adding the compound I and the pinacol diboron, and carrying out a first stirring reaction at room temperature, wherein in the reaction process, a substrate (namely the compound I) and the pinacol diboron (B) are catalyzed by the chitosan/polyvinyl alcohol immobilized nano-copper composite membrane (CP @ Cu NPs)2(pin)2) Adsorbing the catalyst on the surface of the catalyst to be close to each other, forming a complex metal complex by copper and the diboron acid pinacol ester, carrying out addition on a substrate, transferring a boron group connected with the copper to the substrate in a six-membered ring transition state, and selectively finishing the direct boron addition process to obtain the organic boron compound.
Then, after the first stirring reaction is finished, filtering the reaction system to remove the catalyst in the system, washing the filtrate with tetrahydrofuran to obtain an intermediate system with an organic boron compound, directly adding sodium perborate tetrahydrate into the intermediate system, and carrying out a second stirring reaction at room temperature, wherein the reaction equations generated in the processes of the first stirring reaction and the second stirring reaction are as follows:
after the reaction is finished, adding ethyl acetate into the reaction system for dilution, then extracting by taking the ethyl acetate as a solvent, separating out an organic phase, drying by using anhydrous sodium sulfate, then filtering, carrying out rotary evaporation to remove the solvent, carrying out column chromatography on the residue by using mixed solvents of ethyl acetate and petroleum ether in different proportions, and separating and purifying to obtain a beta-hydroxy compound; the proportion of the mixed solvent of the ethyl acetate and the petroleum ether is selected according to different polarities of the product, and silica gel is used as a stationary phase for column chromatography.
In the structural formula (I) and the structural formula (II), the R group can be any one of a phenyl ketone group, a p-halophenyl ketone group, a p-methylphenyl ketone group, a p-methoxy phenyl ketone group, an acyl group, an ester group and a cyano group, and during actual preparation, reaction raw materials with different groups are correspondingly selected according to different product requirements. Further, when the R group is a p-halophenonyl group, it is more preferably a p-fluorophenonyl group or a p-chlorophenoxy group; alternatively, when the R group is acyl, acetyl is more preferred; alternatively, when the R group is an ester group, it is more preferably a methyl ester group or an ethyl ester group.
Further, the addition ratio relationship of each raw material in the reaction is preferably as follows: the ratio of the amount of the substance of the compound I to the volume of the water is 1-2 mmol: 10mL, more preferably 1 mmol: 10 mL; and/or the mass ratio of the compound I to the pinacol ester diborate is (1.2-2.0): 1, more preferably 1.2: 1; and/or the mass ratio of the substance of the compound I to the catalyst is 1-2 mmol: 25mg, more preferably 1 mmol: 25 mg; and/or the mass ratio of the compound I to the sodium perborate tetrahydrate is 1: 4. Under the condition of the addition proportion, the compound I and the diboron pinacol ester can fully react under the action of a catalyst to generate an organic boron compound, and the organic boron compound can fully react with sodium perborate to generate a beta-hydroxy compound, so that the reaction rate is high, and the efficiency is high.
The first stirring reaction and the second stirring reaction are carried out at room temperature, external heating is not needed, and the process cost is favorably reduced. Further, in order to ensure the smooth reaction, the first stirring reaction is preferably carried out at the room temperature of 20-25 ℃, and the reaction time is 10-14 h; and/or carrying out the second stirring reaction at the room temperature of 20-25 ℃, wherein the reaction time is 3-5 h, so that the influence on the reaction efficiency when the room temperature is too high or too low is avoided.
Furthermore, the present invention also provides a pharmaceutical preparation, which comprises a β -hydroxy compound, wherein the β -hydroxy compound is prepared by the above-mentioned preparation method of the β -hydroxy compound, the pharmaceutical preparation includes but is not limited to a pharmaceutical preparation for treating brain tumor and/or cancer, and the pharmaceutical preparation can be added with auxiliary components such as a carrier besides the β -hydroxy compound as an active ingredient, which is not described herein again.
The technical solutions of the present invention are further described in detail with reference to the following specific examples, which should be understood as merely illustrative and not limitative.
EXAMPLE 1 preparation of organoboron Compound
(1) The structural formula of the organoboron compound II-1 is as follows:
(2) a process for producing the organoboron compound II-1:
a. adding 5mg of chitosan/polyvinyl alcohol immobilized nano-copper composite membrane catalyst (CP @ Cu NPs) into a 2.5mL reaction tube, adding 2.0mL of water, and stirring at room temperature (20 ℃, 22 ℃, 24 ℃ or 25 ℃) for 1 h;
b. adding chemical combination into the stirred system respectively and continuously in turnSubstance I-1(38.4mg, 0.2mmol) and pinacol diboron (B)2(pin)2) (60.9mg, 0.24mmol), and the whole system is stirred and reacted for 10h, 11h, 12h, 13h or 14h at room temperature;
c. after the reaction is finished, the whole reaction system is filtered, the filtrate is washed by 3mL of tetrahydrofuran, then an organic phase is separated, and anhydrous Na is used2SO4Drying, filtering, rotary evaporating to remove solvent, purifying the residue by ethyl acetate/petroleum ether mixed solvent (v/v) ═ 6:1 column chromatography to obtain organic boron compound II-138.3 mg, and obtaining the yield>99％。
The mass spectrum detection results are as follows:
1H NMR(400MHz)；δ＝7.68(s,1H),7.41–7.27(m,5H),3.80(s,3H),2.14(s,2H),1.59(s,1H),1.23(s,12H).
13C NMR(100MHz)；δ＝169.09,137.59,136.14,130.05,129.36,128.28,128.02,83.44,24.66.
EXAMPLE 2 preparation of organoboron Compound
(1) The structural formula of the organoboron compound II-2 is as follows:
(2) the preparation method of the organoboron compound II-2 comprises the following steps: the same as in example 1 except that Compound I-1 was replaced with Compound I-2.
The organoboron compound II-2 yield was > 99%.
EXAMPLE 3 preparation of organoboron Compound
(1) The structural formula of the organoboron compound II-3 is as follows:
(2) the preparation method of the organoboron compound II-3 comprises the following steps: the same as in example 1, except that the compound I-1 was replaced with the compound I-3 and the ratio of the compound I-3 to water was 2 mmol: 10mL, the ratio of compound I-3 to catalyst was 2 mmol: 25 mg.
The organoboron compound II-3 yield is > 99%.
EXAMPLE 4 preparation of organoboron Compound
(1) The organoboron compound II-4 has the following structural formula:
(2) the preparation method of the organoboron compound II-4 comprises the following steps: the same as in example 1, except that the compound I-1 was replaced with the compound I-4 and the ratio of the compound I-4 to water was 1.5 mmol: 10mL, compound I-4 to catalyst ratio of 1.5 mmol: 25 mg.
The organoboron compound II-4 yield is > 99%.
EXAMPLE 5 preparation of organoboron Compound
(1) The structural formula of the organoboron compound II-5 is as follows:
(2) the preparation method of the organoboron compound II-5 comprises the following steps: the same as in example 1, except that Compound I-1 was replaced with Compound I-5.
The yield of organoboron compound II-5 is > 99%.
EXAMPLE 6 preparation of organoboron Compound
(1) The organoboron compound II-6 has the following structural formula:
(2) the preparation method of the organoboron compound II-6 comprises the following steps: the same as in example 1, except that Compound I-1 was replaced with Compound I-6.
The organoboron compound II-6 yield is > 99%.
EXAMPLE 7 preparation of organoboron Compound
(1) The organoboron compound II-7 has the following structural formula:
(2) the preparation method of the organoboron compound II-7 comprises the following steps: the same as in example 1, except that Compound I-1 was replaced with Compound I-7.
The organoboron compound II-7 yield is > 99%.
EXAMPLE 8 preparation of organoboron Compound
(1) The structural formula of the organoboron compound II-8 is as follows:
(2) the preparation method of the organoboron compound II-8 comprises the following steps: the same as in example 1, except that Compound I-1 was replaced with Compound I-8.
The yield of organoboron compound II-8 is > 99%.
EXAMPLE 9 preparation of organoboron Compound
(1) The organoboron compound II-9 has the following structural formula:
(2) the preparation method of the organoboron compound II-9: the same as in example 1, except that Compound I-1 was replaced with Compound I-9.
The organoboron compound II-9 yield is > 99%.
EXAMPLE 10 preparation of organoboron Compound
(1) The structural formula of the organoboron compound II-10 is as follows:
(2) the preparation method of the organoboron compound II-10 comprises the following steps: the same as in example 1, except that Compound I-1 was replaced with Compound I-10.
The yield of organoboron compound II-10 was > 99%.
EXAMPLE 11 preparation of organoboron Compound
(1) The structural formula of the organoboron compound II-11 is as follows:
(2) the preparation method of the organoboron compound II-11: the same as in example 1, except that Compound I-1 was replaced with Compound I-11.
The yield of the organoboron compound II-11 was > 99%.
EXAMPLE 12 preparation of organoboron Compound
(1) The organoboron compound II-12 has the following structural formula:
(2) the preparation method of the organoboron compound II-12: the same as in example 1, except that Compound I-1 was replaced with Compound I-12.
The organoboron compound II-12 yield is > 99%.
EXAMPLE 13 preparation of organoboron Compound
(1) The structural formula of the organoboron compound II-13 is as follows:
(2) the preparation method of the organoboron compound II-13: the same as in example 1, except that Compound I-1 was replaced with Compound I-13.
The yield of the organoboron compound II-13 is > 99%.
EXAMPLE 14 preparation of organoboron Compound
(1) The organoboron compound II-14 has the following structural formula:
(2) the preparation method of the organoboron compound II-14: the same as in example 1, except that Compound I-1 was replaced with Compound I-14.
The organoboron compound II-14 yield is > 99%.
EXAMPLE 15 preparation of organoboron Compound
(1) The structural formula of the organoboron compound II-1 is as follows:
(2) a process for producing the organoboron compound II-1:
a. 150mg of chitosan/polyvinyl alcohol immobilized nano-copper composite membrane catalyst (CP @ Cu NPs) is added into a 100mL reaction bottle, 60.0mL of water is added, and the mixture is stirred for 1h at room temperature (20 ℃, 22 ℃, 24 ℃ or 25 ℃);
b. to the stirred system, compound I-1(1.152g, 6mmol) and pinacol ester diboron (B) were added successively2(pin)2) (1.827g, 7.2mmol), and the whole system is stirred at room temperature for reaction for 10h, 11h, 12h, 13h or 14 h;
c. after the reaction is finished, the whole reaction system is filtered, the filtrate is washed by 3mL of tetrahydrofuran, then an organic phase is separated, and anhydrous Na is used2SO4Drying, filtering, rotary evaporating to remove solvent, and purifying the residue by ethyl acetate/petroleum ether mixed solvent (v/v) ═ 6:1 column chromatography to obtain organoboron compound II-11.15 g with yield>99％。
The mass spectrum detection results are as follows:
1H NMR(400MHz)；δ＝7.68(s,1H),7.41–7.27(m,5H),3.80(s,3H),2.14(s,2H),1.59(s,1H),1.23(s,12H).
13C NMR(100MHz)；δ＝169.09,137.59,136.14,130.05,129.36,128.28,128.02,83.44,24.66.
EXAMPLE 16 preparation of beta-hydroxy Compound
(1) The structural formula of the beta-hydroxy compound III-1 is as follows:
(2) the preparation method of the beta-hydroxy compound III-1 comprises the following steps:
a. adding 5mg of chitosan/polyvinyl alcohol immobilized nano-copper composite membrane catalyst (CP @ Cu NPs) into a 2.5mL reaction tube, adding 2.0mL of water, and stirring at room temperature (20 ℃, 22 ℃, 24 ℃ or 25 ℃) for 1 h;
b. to the stirred system, Compound I-1(38.4mg, 0.2mmol) and pinacol ester diboron (B) were added successively2(pin)2) (60.9mg, 0.24mmol), and the whole system is stirred and reacted for 10h, 11h, 12h, 13h or 14h at room temperature;
c. after the reaction is finished, filtering the whole reaction system, washing the filtrate by using 3mL of tetrahydrofuran, then adding sodium perborate tetrahydrate (244mg, 0.8mmol) into the washed filtrate, stirring the whole system at room temperature for reacting for 3h, 4h or 5h, then adding 3mL of ethyl acetate into the reaction system for diluting, extracting by using ethyl acetate (3X 10mL), separating an organic phase, and using anhydrous Na2SO4Drying, filtering, rotary evaporating to remove solvent, and purifying the residue by ethyl acetate/petroleum ether mixed solvent (v/v) ═ 6:1 column chromatography to obtain beta-hydroxy compound III-138.3 mg with high yield>99％。
The mass spectrum detection results are as follows:
1H NMR(400MHz)；δ＝7.84(s,1H),7.47–7.34(m,5H),4.49(s,2H),3.86(s,3H).
13C NMR(100MHz)；δ＝168.41,142.63,134.46,130.83,129.55,129.23,128.57,57.90,52.19.
EXAMPLE 17 preparation of beta-hydroxy Compound
(1) The structural formula of the beta-hydroxy compound III-2 is as follows:
(2) the preparation method of the beta-hydroxy compound III-2 comprises the following steps:
a. adding 5mg of chitosan/polyvinyl alcohol immobilized nano-copper composite membrane catalyst (CP @ Cu NPs) into a 2.5mL reaction tube, adding 2.0mL of water, and stirring at room temperature (20 ℃, 22 ℃, 24 ℃ or 25 ℃) for 1 h;
b. to the stirred system, compound I-2(38.4mg, 0.2mmol) and pinacol ester diboron (B) were added successively2(pin)2) (60.9mg, 0.24mmol), and the whole system is stirred at room temperature for reaction for 11h, 12h or 13 h;
c. after the reaction is finished, filtering the whole reaction system, washing the filtrate by using 3mL of tetrahydrofuran, then adding sodium perborate tetrahydrate (244mg, 0.8mmol) into the washed filtrate, stirring the whole system at room temperature for reacting for 3h, 4h or 5h, then adding 3mL of ethyl acetate into the reaction system for diluting, extracting by using ethyl acetate (3X 10mL), separating an organic phase, and using anhydrous Na2SO4Drying, filtering, rotary evaporation to remove solvent, and column chromatography of the residue on ethyl acetate/petroleum ether mixed solvent (v/v) ═ 6:1 to give β -hydroxy compound III-237.8 mg, 90% yield.
The mass spectrum detection results are as follows:
1H NMR(400MHz)；δ＝7.79(s,1H),7.49–7.45(m,2H),7.13(t,J＝8.6Hz,2H),4.46(s,2H),3.86(s,3H).
13C NMR(100MHz)；δ＝168.32,164.48,161.99,141.66,131.72,131.63,130.62,130.57,115.90,115.69,57.83,52.30.
EXAMPLE 18 preparation of beta-hydroxy Compound
(1) The structural formula of the beta-hydroxy compound III-3 is as follows:
(2) the preparation method of the beta-hydroxy compound III-3 comprises the following steps:
a. adding 5mg of chitosan/polyvinyl alcohol immobilized nano-copper composite membrane catalyst (CP @ Cu NPs) into a 2.5mL reaction tube, adding 2.0mL of water, and stirring at room temperature (20 ℃, 22 ℃, 24 ℃ or 25 ℃) for 1 h;
b. to the stirred system, compound I-3(48.5mg, 0.2mmol) and pinacol ester diboron (B) were added successively2(pin)2) (60.9mg, 0.24mmol), and the whole system is stirred and reacts for 12h at room temperature;
c. after the reaction, the whole reaction system was filtered, the filtrate was washed with 3mL of tetrahydrofuran, then sodium perborate tetrahydrate (244mg, 0.8mmol) was added to the washed filtrate, the whole system was stirred at room temperature for 4h, then 3mL of ethyl acetate was added to the reaction system for dilution, extraction was performed with ethyl acetate (3X 10mL), the organic phase was separated, and anhydrous Na was used for extraction2SO4Drying, filtering, rotary evaporation to remove the solvent, and purification of the residue by column chromatography using ethyl acetate/petroleum ether mixed solvent (v/v) ═ 6:1 to give β -hydroxy compound III-341.9 mg, 91% yield.
The mass spectrum detection results are as follows:
1H NMR(400MHz)；δ＝7.77(s,1H),7.42–7.37(m,4H),4.44(s,2H),3.86(s,3H).
13C NMR(100MHz)；δ＝168.15,141.38,135.38,132.87,131.29,130.90,128.87,57.72,52.28.
EXAMPLE 19 preparation of beta-hydroxy Compound
(1) The structural formula of the beta-hydroxy compound III-4 is as follows:
(2) the preparation method of the beta-hydroxy compound III-4 comprises the following steps:
a. adding 5mg of chitosan/polyvinyl alcohol immobilized nano-copper composite membrane catalyst (CP @ Cu NPs) into a 2.5mL reaction tube, adding 2.0mL of water, and stirring at room temperature (20 ℃, 22 ℃, 24 ℃ or 25 ℃) for 1 h;
b. to the stirred system, compound I-4(48.5mg, 0.2mmol) and pinacol ester diboron (B) were added successively2(pin)2) (60.9mg, 0.24mmol), and the whole system is stirred and reacts for 12h at room temperature;
c. after the reaction, the whole reaction system was filtered, the filtrate was washed with 3mL of tetrahydrofuran, then sodium perborate tetrahydrate (244mg, 0.8mmol) was added to the washed filtrate, the whole system was stirred at room temperature for 4h, then 3mL of ethyl acetate was added to the reaction system for dilution, extraction was performed with ethyl acetate (3X 10mL), the organic phase was separated, and anhydrous Na was used for extraction2SO4Drying, filtering, rotary evaporation to remove solvent, and column chromatography of the residue on ethyl acetate/petroleum ether mixed solvent (v/v) ═ 6:1 to give β -hydroxy compound III-441.1 mg, in > 99% yield.
The mass spectrum detection results are as follows:
1H NMR(400MHz)；δ＝7.81(s,1H),7.38(d,J＝8.1Hz,2H),7.23(d,J＝7.9Hz,2H),4.50(s,2H),3.85(s,3H),2.38(s,3H).
13C NMR(100MHz)；δ＝168.54,142.76,139.59,131.61,129.95,129.67,129.32,57.98,52.13,21.38.
EXAMPLE 20 preparation of beta-hydroxy Compound
(1) The structural formula of the beta-hydroxy compound III-5 is as follows:
(2) the preparation method of the beta-hydroxy compound III-5 comprises the following steps:
a. adding 5mg of chitosan/polyvinyl alcohol immobilized nano-copper composite membrane catalyst (CP @ Cu NPs) into a 2.5mL reaction tube, adding 2.0mL of water, and stirring at room temperature (20 ℃, 22 ℃, 24 ℃ or 25 ℃) for 1 h;
b. to the stirred system, compound I-5(48.5mg, 0.2mmol) and pinacol ester diboron (B) were added successively2(pin)2) (60.9mg, 0.24mmol), and the whole system is stirred and reacts for 12h at room temperature;
c. after the reaction, the whole reaction system was filtered, the filtrate was washed with 3mL of tetrahydrofuran, then sodium perborate tetrahydrate (244mg, 0.8mmol) was added to the washed filtrate, the whole system was stirred at room temperature for 4h, then 3mL of ethyl acetate was added to the reaction system for dilution, extraction was performed with ethyl acetate (3X 10mL), the organic phase was separated, and anhydrous Na was used for extraction2SO4Drying, filtering, rotary evaporation to remove the solvent, and purification of the residue by column chromatography using ethyl acetate/petroleum ether mixed solvent (v/v) ═ 6:1 to give β -hydroxy compound III-548.3 mg, 92% yield.
The mass spectrum detection results are as follows:
1H NMR(400MHz)；δ＝7.82(s,1H),7.67(d,J＝8.2Hz,2H),7.58–7.55(m,2H),4.43(s,2H),3.87(s,3H).
13C NMR(100MHz)；δ＝167.91,140.84,137.96,137.95,132.79,131.05,130.73,129.71,125.18,57.56,52.36.
EXAMPLE 21 preparation of beta-hydroxy Compound
(1) The structural formula of the beta-hydroxy compound III-6 is as follows:
(2) the preparation method of the beta-hydroxy compound III-6 comprises the following steps:
a. adding 5mg of chitosan/polyvinyl alcohol immobilized nano-copper composite membrane catalyst (CP @ Cu NPs) into a 2.5mL reaction tube, adding 2.0mL of water, and stirring at room temperature (20 ℃, 22 ℃, 24 ℃ or 25 ℃) for 1 h;
b. to the stirred system, Compound I-6(48.5mg, 0.2mmol) and pinacol ester diboron (B) were added successively2(pin)2) (60.9mg, 0.24mmol), and the whole system is stirred and reacts for 12h at room temperature;
c. after the reaction is finished, filtering the whole reaction system, washing the filtrate by using 3mL of tetrahydrofuran, and then adding perborate into the washed filtrateSodium tetrahydrate (244mg, 0.8mmol), the whole was stirred at room temperature for reaction for 4 hours, then ethyl acetate (3 mL) was added to the reaction system for dilution, extraction was performed with ethyl acetate (3X 10mL), the organic phase was separated, and anhydrous Na was used2SO4Drying, filtration, rotary evaporation to remove the solvent and purification of the residue by column chromatography over ethyl acetate/petroleum ether mixed solvent (v/v) ═ 6:1 gave β -hydroxy compound III-640.9 mg, 91% yield.
The mass spectrum detection results are as follows:
1H NMR(400MHz)；δ＝7.97(s,1H),7.43–7.33(m,2H),6.99(t,J＝7.6Hz,1H),6.91(dd,J＝8.3,1.0Hz,1H),4.43(s,2H),3.86(s,6H).
13C NMR(100MHz)；δ＝168.67,160.58,142.65,131.56,128.68,127.01,114.09,58.02,55.34,52.10.
EXAMPLE 22 preparation of beta-hydroxy Compound
(1) The structural formula of the beta-hydroxy compound III-7 is as follows:
(2) the preparation method of the beta-hydroxy compound III-7 comprises the following steps:
a. adding 5mg of chitosan/polyvinyl alcohol immobilized nano-copper composite membrane catalyst (CP @ Cu NPs) into a 2.5mL reaction tube, adding 2.0mL of water, and stirring at room temperature (20 ℃, 22 ℃, 24 ℃ or 25 ℃) for 1 h;
b. to the stirred system, Compound I-7(48.5mg, 0.2mmol) and pinacol ester diboron (B) were added successively2(pin)2) (60.9mg, 0.24mmol), and the whole system is stirred and reacts for 12h at room temperature;
c. after the reaction, the whole reaction system is filtered, the filtrate is washed by 3mL of tetrahydrofuran, then sodium perborate tetrahydrate (244mg, 0.8mmol) is added into the washed filtrate, the whole system is stirred and reacted for 4 hours at room temperature, then 3mL of ethyl acetate is added into the reaction system for dilution, extraction is carried out by ethyl acetate (3X 10mL), an organic phase is separated, and anhydrous is used for extractingNa2SO4Drying, filtering, rotary evaporation to remove solvent, and column chromatography of the residue on ethyl acetate/petroleum ether mixed solvent (v/v) ═ 6:1 to give β -hydroxy compound III-744.0 mg, in > 99% yield.
The mass spectrum detection results are as follows:
1H NMR(400MHz)；δ＝7.82(s,1H),7.40(d,J＝7.9Hz,2H),7.26–7.23(m,2H),4.51(s,2H),3.86(s,3H),2.71(q,J＝7.6Hz,2H),1.27(t,J＝7.6Hz,3H.
13C NMR(100MHz)；δ＝168.57,145.88,142.78,131.86,129.99,129.77,128.15,58.02,52.14,28.73,15.36.
EXAMPLE 23 preparation of beta-hydroxy Compound
(1) The structural formula of the beta-hydroxy compound III-8 is as follows:
(2) the preparation method of the beta-hydroxy compound III-8 comprises the following steps:
a. adding 5mg of chitosan/polyvinyl alcohol immobilized nano-copper composite membrane catalyst (CP @ Cu NPs) into a 2.5mL reaction tube, adding 2.0mL of water, and stirring at room temperature (20 ℃, 22 ℃, 24 ℃ or 25 ℃) for 1 h;
b. to the stirred system, Compound I-8(48.5mg, 0.2mmol) and pinacol ester diboron (B) were added successively2(pin)2) (60.9mg, 0.24mmol), and the whole system is stirred and reacts for 12h at room temperature;
c. after the reaction, the whole reaction system was filtered, the filtrate was washed with 3mL of tetrahydrofuran, then sodium perborate tetrahydrate (244mg, 0.8mmol) was added to the washed filtrate, the whole system was stirred at room temperature for 4h, then 3mL of ethyl acetate was added to the reaction system for dilution, extraction was performed with ethyl acetate (3X 10mL), the organic phase was separated, and anhydrous Na was used for extraction2SO4Drying, filtering, rotary evaporating to remove solvent, purifying the residue by ethyl acetate/petroleum ether mixed solvent (v/v) ═ 6:1 column chromatography to obtain beta-hydroxy compound III-846.7 mg,the yield was 93%.
The mass spectrum detection results are as follows:
1H NMR(400MHz)；δ＝7.79(s,1H),7.49–7.45(m,2H),7.13(t,J＝8.6Hz,2H),4.46(s,2H),3.86(s,3H).
13C NMR(100MHz)；δ＝168.32,164.48,161.99,141.66,131.72,131.63,130.62,130.57,115.90,115.69,57.83,52.30.
EXAMPLE 24 preparation of beta-hydroxy Compound
(1) The structural formula of the beta-hydroxy compound III-9 is as follows:
(2) the preparation method of the beta-hydroxy compound III-9 comprises the following steps:
a. adding 5mg of chitosan/polyvinyl alcohol immobilized nano-copper composite membrane catalyst (CP @ Cu NPs) into a 2.5mL reaction tube, adding 2.0mL of water, and stirring at room temperature (20 ℃, 22 ℃, 24 ℃ or 25 ℃) for 1 h;
b. to the stirred system, compound I-9(48.5mg, 0.2mmol) and pinacol ester diboron (B) were added successively2(pin)2) (60.9mg, 0.24mmol), and the whole system is stirred and reacts for 12h at room temperature;
c. after the reaction, the whole reaction system was filtered, the filtrate was washed with 3mL of tetrahydrofuran, then sodium perborate tetrahydrate (244mg, 0.8mmol) was added to the washed filtrate, the whole system was stirred at room temperature for 4h, then 3mL of ethyl acetate was added to the reaction system for dilution, extraction was performed with ethyl acetate (3X 10mL), the organic phase was separated, and anhydrous Na was used for extraction2SO4Drying, filtering, rotary evaporation to remove solvent, and column chromatography of the residue on ethyl acetate/petroleum ether mixed solvent (v/v) ═ 6:1 to give β -hydroxy compound III-954.2 mg, in > 99% yield.
The mass spectrum detection results are as follows:
1H NMR(400MHz)；δ＝7.74(s,1H),7.59(d,J＝1.7Hz,1H),7.52–7.50(m,1H),7.41–7.38(m,1H),7.31–7.27(m,2H),4.45(s,2H),3.87(s,3H).
13C NMR(100MHz)；δ＝168.00,140.84,136.48,132.24,132.14,132.10,130.12,128.02,122.66,57.72,52.34.
EXAMPLE 25 preparation of beta-hydroxy Compound
(1) The structural formula of the beta-hydroxy compound III-10 is as follows:
(2) the preparation method of the beta-hydroxy compound III-10 comprises the following steps:
a. adding 5mg of chitosan/polyvinyl alcohol immobilized nano-copper composite membrane catalyst (CP @ Cu NPs) into a 2.5mL reaction tube, adding 2.0mL of water, and stirring at room temperature (20 ℃, 22 ℃, 24 ℃ or 25 ℃) for 1 h;
b. to the stirred system, compound I-10(48.5mg, 0.2mmol) and pinacol ester diboron (B) were added successively2(pin)2) (60.9mg, 0.24mmol), and the whole system is stirred and reacts for 12h at room temperature;
c. after the reaction, the whole reaction system was filtered, the filtrate was washed with 3mL of tetrahydrofuran, then sodium perborate tetrahydrate (244mg, 0.8mmol) was added to the washed filtrate, the whole system was stirred at room temperature for 4h, then 3mL of ethyl acetate was added to the reaction system for dilution, extraction was performed with ethyl acetate (3X 10mL), the organic phase was separated, and anhydrous Na was used for extraction2SO4Drying, filtration, rotary evaporation to remove the solvent and purification of the residue by column chromatography over ethyl acetate/petroleum ether mixed solvent (v/v) ═ 6:1 gave β -hydroxy compound III-1043.2 mg, 94% yield.
The mass spectrum detection results are as follows:
1H NMR(400MHz)；δ＝7.79(s,1H),7.49(dd,J＝8.5,5.5Hz,2H),7.11(t,J＝8.7Hz,2H),4.46(s,2H),3.86(s,3H).
13C NMR(100MHz)；δ＝168.28,164.46,161.97,141.61,131.68,131.60,130.63,115.86,115.65,57.79,52.24.
EXAMPLE 26 preparation of beta-hydroxy Compound
(1) The structural formula of the beta-hydroxy compound III-11 is as follows:
(2) the preparation method of the beta-hydroxy compound III-11 comprises the following steps:
a. adding 5mg of chitosan/polyvinyl alcohol immobilized nano-copper composite membrane catalyst (CP @ Cu NPs) into a 2.5mL reaction tube, adding 2.0mL of water, and stirring at room temperature (20 ℃, 22 ℃, 24 ℃ or 25 ℃) for 1 h;
b. to the stirred system, Compound I-11(48.5mg, 0.2mmol) and pinacol ester diboron (B) were added successively2(pin)2) (60.9mg, 0.24mmol), and the whole system is stirred and reacts for 12h at room temperature;
c. after the reaction, the whole reaction system was filtered, the filtrate was washed with 3mL of tetrahydrofuran, then sodium perborate tetrahydrate (244mg, 0.8mmol) was added to the washed filtrate, the whole system was stirred at room temperature for 4h, then 3mL of ethyl acetate was added to the reaction system for dilution, extraction was performed with ethyl acetate (3X 10mL), the organic phase was separated, and anhydrous Na was used for extraction2SO4Drying, filtration, rotary evaporation to remove the solvent and purification of the residue by column chromatography over ethyl acetate/petroleum ether mixed solvent (v/v) ═ 6:1 gave β -hydroxy compound III-1143.1 mg, 85% yield.
The mass spectrum detection results are as follows:
1H NMR(400MHz)；δ＝7.80(s,1H),7.11–7.09(m,2H),6.92(d,J＝8.8Hz,1H),4.52(s,2H),3.92(d,J＝4.3Hz,6H),3.86(s,3H).
13C NMR(100MHz)；δ＝168.61,150.15,148.81,143.02,128.86,127.27,123.36,112.61,110.90,58.07,55.92,55.89,52.15.
EXAMPLE 27 preparation of beta-hydroxy Compound
(1) The structural formula of the beta-hydroxy compound III-12 is as follows:
(2) the preparation method of the beta-hydroxy compound III-12 comprises the following steps:
a. adding 5mg of chitosan/polyvinyl alcohol immobilized nano-copper composite membrane catalyst (CP @ Cu NPs) into a 2.5mL reaction tube, adding 2.0mL of water, and stirring at room temperature (20 ℃, 22 ℃, 24 ℃ or 25 ℃) for 1 h;
b. to the stirred system, Compound I-12(48.5mg, 0.2mmol) and pinacol ester diboron (B) were added successively2(pin)2) (60.9mg, 0.24mmol), and the whole system is stirred and reacts for 12h at room temperature;
c. after the reaction, the whole reaction system was filtered, the filtrate was washed with 3mL of tetrahydrofuran, then sodium perborate tetrahydrate (244mg, 0.8mmol) was added to the washed filtrate, the whole system was stirred at room temperature for 4h, then 3mL of ethyl acetate was added to the reaction system for dilution, extraction was performed with ethyl acetate (3X 10mL), the organic phase was separated, and anhydrous Na was used for extraction2SO4Drying, filtration, rotary evaporation to remove the solvent and purification of the residue by column chromatography over ethyl acetate/petroleum ether mixed solvent (v/v) ═ 6:1 gave β -hydroxy compound III-1234.9 mg, 88% yield.
The mass spectrum detection results are as follows:
1H NMR(400MHz)；δ＝6.70(d,J＝10.0Hz,1H),4.31(s,2H),3.75(s,3H),2.56(s,1H),2.47–2.41(m,1H),1.74–1.61(m,4H),1.34–1.10(m,6H).
13C NMR(100MHz)；δ＝168.28,150.86,128.95,57.38,51.79,37.39,32.26,25.59,25.28.
EXAMPLE 28 preparation of beta-hydroxy Compound
(1) The structural formula of the beta-hydroxy compound III-13 is as follows:
(2) the preparation method of the beta-hydroxy compound III-13 comprises the following steps:
a. adding 5mg of chitosan/polyvinyl alcohol immobilized nano-copper composite membrane catalyst (CP @ Cu NPs) into a 2.5mL reaction tube, adding 2.0mL of water, and stirring at room temperature (20 ℃, 22 ℃, 24 ℃ or 25 ℃) for 1 h;
b. to the stirred system, Compound I-13(48.5mg, 0.2mmol) and pinacol ester diboron (B) were added successively2(pin)2) (60.9mg, 0.24mmol), and the whole system is stirred and reacts for 12h at room temperature;
c. after the reaction, the whole reaction system was filtered, the filtrate was washed with 3mL of tetrahydrofuran, then sodium perborate tetrahydrate (244mg, 0.8mmol) was added to the washed filtrate, the whole system was stirred at room temperature for 4h, then 3mL of ethyl acetate was added to the reaction system for dilution, extraction was performed with ethyl acetate (3X 10mL), the organic phase was separated, and anhydrous Na was used for extraction2SO4Drying, filtration, rotary evaporation to remove the solvent and purification of the residue by column chromatography over ethyl acetate/petroleum ether mixed solvent (v/v) ═ 6:1 gave β -hydroxy compound III-1330.2 mg, 81% yield.
The mass spectrum detection results are as follows:
1H NMR(400MHz)；δ＝6.90(t,J＝7.8Hz,1H),4.32(s,2H),3.76(s,3H),2.28(q,J＝7.6Hz,2H),1.47(p,J＝7.3Hz,2H),1.30–1.27(m,4H),0.89–0.85(m,3H).
13C NMR(100MHz)；δ＝168.09,146.20,130.69,57.22,51.88,31.43,28.46,28.33,22.43,13.96.
EXAMPLE 29 preparation of beta-hydroxy Compound
(1) The structural formula of the beta-hydroxy compound III-14 is as follows:
(2) the preparation method of the beta-hydroxy compound III-14 comprises the following steps:
a. adding 5mg of chitosan/polyvinyl alcohol immobilized nano-copper composite membrane catalyst (CP @ Cu NPs) into a 2.5mL reaction tube, adding 2.0mL of water, and stirring at room temperature (20 ℃, 22 ℃, 24 ℃ or 25 ℃) for 1 h;
b. to the stirred system, Compound I-14(48.5mg, 0.2mmol) and pinacol ester diboron (B) were added successively2(pin)2) (60.9mg, 0.24mmol), and the whole system is stirred and reacts for 12h at room temperature;
c. after the reaction, the whole reaction system was filtered, the filtrate was washed with 3mL of tetrahydrofuran, then sodium perborate tetrahydrate (244mg, 0.8mmol) was added to the washed filtrate, the whole system was stirred at room temperature for 4h, then 3mL of ethyl acetate was added to the reaction system for dilution, extraction was performed with ethyl acetate (3X 10mL), the organic phase was separated, and anhydrous Na was used for extraction2SO4Drying, filtration, rotary evaporation to remove the solvent and purification of the residue by column chromatography over ethyl acetate/petroleum ether mixed solvent (v/v) ═ 6:1 gave β -hydroxy compound III-1424.7 mg, 79% yield.
The mass spectrum detection results are as follows:
1H NMR(400MHz)；δ＝6.69(d,J＝10.1Hz,1H),4.34(s,2H),3.78(s,3H),2.78(dp,J＝10.2,6.6Hz,1H),1.05(d,J＝6.6Hz,6H).
13C NMR(100MHz)；δ＝168.28,152.29,128.57,57.45,51.87,27.72,22.37.
the above is only a preferred embodiment of the present invention, and it is not intended to limit the scope of the invention, and various modifications and changes will occur to those skilled in the art. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention shall be included in the scope of the present invention.
Claims (10)
1. A process for producing an organoboron compound, characterized by comprising the steps of:
stirring a compound I, pinacol diboron, a catalyst and water at room temperature for reaction, and separating and purifying a reaction product after the reaction is finished to obtain an organic boron compound;
the structural formula of the compound I is shown as the following structural formula (I), the structural general formula of the organic boron compound is shown as the following structural formula (II), and the catalyst is a chitosan/polyvinyl alcohol immobilized nano copper composite membrane;
in the structural formula (I) and the structural formula (II), R groups are phenyl ketone groups, p-halogenophenyl ketone groups, p-methyl phenyl ketone groups, p-methoxy phenyl ketone groups, acyl groups, ester groups or cyano groups.
2. A process for producing an organoboron compound of claim 1, wherein the p-halophenonyl group is a p-fluorophenonyl group or a p-chlorophenoxyl group; alternatively, the first and second electrodes may be,
the acyl group is acetyl; alternatively, the first and second electrodes may be,
the ester group is a methyl ester group or an ethyl ester group.
3. A process for producing an organoboron compound as claimed in claim 1, wherein the ratio of the amount of the substance of the compound I to the volume of the water is 1 to 2 mmol: 10 mL; and/or the presence of a gas in the gas,
the mass ratio of the compound I to the pinacol ester diborate is (1.2-2.0): 1; and/or the presence of a gas in the gas,
the mass ratio of the substance of the compound I to the catalyst is 1-2 mmol: 25 mg; and/or the presence of a gas in the gas,
the reaction temperature of the stirring reaction is 20-25 ℃, and the reaction time is 10-14 h.
4. The process for producing an organoboron compound according to claim 1, wherein the step of separating and purifying the reaction product after the completion of the reaction to obtain the organoboron compound comprises:
and after the reaction is finished, filtering the reaction system to remove the catalyst, washing the filtrate by adopting tetrahydrofuran, evaporating and concentrating, carrying out column chromatography on the concentrated residue by using a mixed solvent of ethyl acetate and petroleum ether, and purifying to obtain the organic boron compound.
5. A pharmaceutical preparation comprising an organoboron compound produced by the process for producing an organoboron compound according to any one of claims 1 to 4.
6. A process for the preparation of a β -hydroxy compound, comprising the steps of:
carrying out a first stirring reaction on the compound I, the diboron pinacol ester, a catalyst and water at room temperature, and removing the catalyst after the reaction is finished to obtain an intermediate system with an organic boron compound;
adding sodium perborate tetrahydrate into the intermediate system, carrying out a second stirring reaction at room temperature, and separating and purifying a reaction product after the reaction is finished to obtain a beta-hydroxy compound;
the structural formula of the compound I is shown as the following structural formula (I), the structural general formula of the organic boron compound is shown as the following structural formula (II), the structural general formula of the beta-hydroxyl compound is shown as the following structural formula (III), and the catalyst is a chitosan/polyvinyl alcohol immobilized nano copper composite membrane;
in the structural formula (II), the structural formula (II) and the structural formula (III), R groups are phenyl ketone groups, p-halogenophenyl ketone groups, p-methyl phenyl ketone groups, p-methoxy phenyl ketone groups, acyl groups, ester groups or cyano groups.
7. The method for producing a β -hydroxy compound according to claim 6, wherein the p-halophenonyl group is a p-fluorophenonyl group or a p-chlorophenoxyyl group; and/or the presence of a gas in the gas,
the acyl group is acetyl; and/or the presence of a gas in the gas,
the ester group is a methyl ester group or an ethyl ester group.
8. The method for producing a β -hydroxy compound according to claim 6, wherein the ratio of the amount of the substance of compound I to the volume of the water is 1 to 2 mmol: 10 mL; and/or the presence of a gas in the gas,
the mass ratio of the compound I to the pinacol ester diborate is (1.2-2.0): 1; and/or the presence of a gas in the gas,
the mass ratio of the substance of the compound I to the catalyst is 1-2 mmol: 25 mg; and/or the presence of a gas in the gas,
the mass ratio of the compound I to the sodium perborate tetrahydrate is 1: 4.
9. The method for preparing a β -hydroxy compound according to claim 6, wherein the reaction temperature of the first stirring reaction is 20 to 25 ℃ and the reaction time is 10 to 14 hours; and/or the presence of a gas in the gas,
the reaction temperature of the second stirring reaction is 20-25 ℃, and the reaction time is 3-5 h.
10. A pharmaceutical preparation comprising a β -hydroxy compound produced by the process for producing a β -hydroxy compound according to any one of claims 6 to 9.
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| CN110590819A (en) * | 2019-08-28 | 2019-12-20 | 湖北工程学院 | Process for producing organoboron compound and process for producing beta-hydroxyorganoboron compound |
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