CN114213440B - 2-boron alkenyl oxygen ether compound and preparation method thereof - Google Patents
2-boron alkenyl oxygen ether compound and preparation method thereof Download PDFInfo
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- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 title claims abstract description 81
- 229910052760 oxygen Inorganic materials 0.000 title claims abstract description 31
- 239000001301 oxygen Substances 0.000 title claims abstract description 31
- 229910052796 boron Inorganic materials 0.000 title claims abstract description 26
- 238000002360 preparation method Methods 0.000 title claims abstract description 15
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 153
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 81
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 72
- 238000006243 chemical reaction Methods 0.000 claims description 58
- 238000004440 column chromatography Methods 0.000 claims description 52
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 44
- -1 cyclohexyl ethynyl phenoxyether Chemical compound 0.000 claims description 39
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 33
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 33
- 239000000741 silica gel Substances 0.000 claims description 33
- 229910002027 silica gel Inorganic materials 0.000 claims description 33
- 239000010949 copper Substances 0.000 claims description 28
- BMIBJCFFZPYJHF-UHFFFAOYSA-N 2-methoxy-5-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine Chemical compound COC1=NC=C(C)C=C1B1OC(C)(C)C(C)(C)O1 BMIBJCFFZPYJHF-UHFFFAOYSA-N 0.000 claims description 27
- 239000002253 acid Substances 0.000 claims description 27
- 239000003208 petroleum Substances 0.000 claims description 26
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 25
- 239000012074 organic phase Substances 0.000 claims description 25
- 239000003960 organic solvent Substances 0.000 claims description 25
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 25
- 238000000605 extraction Methods 0.000 claims description 24
- 239000012071 phase Substances 0.000 claims description 24
- 239000007788 liquid Substances 0.000 claims description 23
- 239000002904 solvent Substances 0.000 claims description 19
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 15
- 238000001035 drying Methods 0.000 claims description 15
- 238000010438 heat treatment Methods 0.000 claims description 14
- 238000002156 mixing Methods 0.000 claims description 10
- 238000001704 evaporation Methods 0.000 claims description 6
- 238000003756 stirring Methods 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 5
- 238000001816 cooling Methods 0.000 claims description 4
- 238000011049 filling Methods 0.000 claims description 3
- 238000001914 filtration Methods 0.000 claims description 3
- 239000000203 mixture Substances 0.000 abstract description 86
- 238000003786 synthesis reaction Methods 0.000 abstract description 10
- 230000015572 biosynthetic process Effects 0.000 abstract description 8
- 150000001875 compounds Chemical class 0.000 abstract description 8
- 239000000126 substance Substances 0.000 abstract description 5
- 239000000758 substrate Substances 0.000 abstract description 5
- 125000000217 alkyl group Chemical group 0.000 abstract description 4
- 125000003172 aldehyde group Chemical group 0.000 abstract description 2
- 125000003118 aryl group Chemical group 0.000 abstract description 2
- 125000004093 cyano group Chemical group *C#N 0.000 abstract description 2
- 125000004185 ester group Chemical group 0.000 abstract description 2
- 229910052736 halogen Inorganic materials 0.000 abstract description 2
- 150000002367 halogens Chemical class 0.000 abstract description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 abstract description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 abstract description 2
- 238000001308 synthesis method Methods 0.000 abstract description 2
- 238000002390 rotary evaporation Methods 0.000 description 34
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
- 238000000967 suction filtration Methods 0.000 description 19
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- 238000001228 spectrum Methods 0.000 description 9
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 8
- 238000005481 NMR spectroscopy Methods 0.000 description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 125000000304 alkynyl group Chemical group 0.000 description 5
- 239000004327 boric acid Substances 0.000 description 5
- 229910052799 carbon Inorganic materials 0.000 description 5
- 239000002994 raw material Substances 0.000 description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 229910052802 copper Inorganic materials 0.000 description 4
- NHOGGUYTANYCGQ-UHFFFAOYSA-N ethenoxybenzene Chemical compound C=COC1=CC=CC=C1 NHOGGUYTANYCGQ-UHFFFAOYSA-N 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- 230000035484 reaction time Effects 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 150000001345 alkine derivatives Chemical class 0.000 description 3
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 3
- 238000006197 hydroboration reaction Methods 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- HXDOZKJGKXYMEW-UHFFFAOYSA-N 4-ethylphenol Chemical compound CCC1=CC=C(O)C=C1 HXDOZKJGKXYMEW-UHFFFAOYSA-N 0.000 description 2
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 150000002170 ethers Chemical class 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 150000002739 metals Chemical class 0.000 description 2
- IWDCLRJOBJJRNH-UHFFFAOYSA-N p-cresol Chemical compound CC1=CC=C(O)C=C1 IWDCLRJOBJJRNH-UHFFFAOYSA-N 0.000 description 2
- IVDFJHOHABJVEH-UHFFFAOYSA-N pinacol Chemical compound CC(C)(O)C(C)(C)O IVDFJHOHABJVEH-UHFFFAOYSA-N 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 description 1
- 239000007818 Grignard reagent Substances 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- 240000006915 Petasites Species 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 238000006161 Suzuki-Miyaura coupling reaction Methods 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 150000001638 boron Chemical class 0.000 description 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- SSDZYLQUYMOSAK-UHFFFAOYSA-N ethynylcyclohexane Chemical group C#CC1CCCCC1 SSDZYLQUYMOSAK-UHFFFAOYSA-N 0.000 description 1
- NPTDXPDGUHAFKC-UHFFFAOYSA-N ethynylcyclopropane Chemical group C#CC1CC1 NPTDXPDGUHAFKC-UHFFFAOYSA-N 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 150000004795 grignard reagents Chemical class 0.000 description 1
- YVXHZKKCZYLQOP-UHFFFAOYSA-N hept-1-yne Chemical compound CCCCCC#C YVXHZKKCZYLQOP-UHFFFAOYSA-N 0.000 description 1
- 238000007172 homogeneous catalysis Methods 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- SKOWZLGOFVSKLB-UHFFFAOYSA-N hypodiboric acid Chemical compound OB(O)B(O)O SKOWZLGOFVSKLB-UHFFFAOYSA-N 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 238000006557 surface reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000006257 total synthesis reaction Methods 0.000 description 1
Classifications
-
- 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
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
- C07F5/02—Boron compounds
- C07F5/025—Boronic and borinic acid compounds
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J23/00—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00
- B01J23/70—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of the iron group metals or copper
- B01J23/72—Copper
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
- B01J31/06—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides containing polymers
- B01J31/069—Hybrid organic-inorganic polymers, e.g. silica derivatized with organic groups
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a 2-boron alkenyl oxygen ether compound and a preparation method thereof, wherein the compound comprises the following chemical formula and acceptable formulaSalts, tautomers, stereoisomers and mixtures thereof in all ratios:wherein R is 1 Is alkyl or aryl; r is R 2 Is one of hydrogen atom, alkyl, methoxy, halogen, cyano, nitro, aldehyde group and ester group. The invention provides a synthesis method of a 2-boron alkenyl oxygen ether compound, which has the advantages of simple operation, simple steps, wide substrate application range, simple post-treatment and capability of amplifying synthesis.
Description
Technical Field
The invention relates to the technical field of compound preparation, in particular to a 2-boron alkenyl oxygen ether compound and a preparation method thereof.
Background
2-boroalkenyloxy ether derivatives are an important class of boron-containing, oxygen-containing compounds, of which organoboronic acids and derivatives thereof are a very useful class of intermediates in organic synthetic chemistry, and in general, organoboron derivatives are used as carbon nucleophiles to introduce functional groups into substrate molecules. Furthermore, the carbon-boron bond may be converted to a carbon-carbon bond or a carbon-heteroatom bond using a Suzuki-Miyaura coupling reaction, petasites reaction, or the like. Compared with organic metals such as organic metals or Grignard reagent, the organic boric acid and the derivative thereof have more excellent properties, have the advantages of stable chemical properties and easy post-treatment due to insensitivity to oxygen and moisture, and have the characteristics of low toxicity, medium reactivity, good functional group compatibility and the like. Among the organic boric acid and the derivatives thereof, the alkenyl boric acid derivatives are organic synthesis intermediates with high application value, can be further converted into various products such as alkenyl halogenide, alkenyl azide, alkenyl cyanide, alkenyl carboxylic acid and the like, and can be used for constructing polysubstituted olefin and widely applied to total synthesis of natural products.
The alkyne hydroboration reaction is adopted to rapidly prepare the alkenyl boric acid compound, wherein copper catalysis alkyne hydroboration reaction is one of the most effective methods for preparing the alkenyl boron derivatives, but the catalyst is difficult to recycle due to homogeneous catalysis of a reaction system, the currently reported heterogeneous copper catalyst synthesis process is complex, the synthesis cost is high, industrial application is difficult, and in addition, the heterogeneous copper catalysis alkynyl oxygen ether substrate hydroboration reaction is not effective for preparing the 2-boron alkenyl oxygen ether derivatives.
Disclosure of Invention
This section is intended to outline some aspects of embodiments of the invention and to briefly introduce some preferred embodiments. Some simplifications or omissions may be made in this section as well as in the description summary and in the title of the application, to avoid obscuring the purpose of this section, the description summary and the title of the invention, which should not be used to limit the scope of the invention.
The present invention has been made in view of the problems involved in the synthesis of 2-boroalkenyloxy ether derivatives.
Therefore, one of the purposes of the invention is to overcome the shortages of the synthesis of the existing 2-boron-based alkenyl oxygen ether derivatives, and provide a 2-boron-based alkenyl oxygen ether derivative compound which comprises the following chemical formula and acceptable salts, tautomers, stereoisomers and mixtures thereof in all proportions:
wherein the method comprises the steps of
R 1 Is alkyl or aryl;
R 2 is one of hydrogen atom, alkyl, methoxy, halogen, cyano, nitro, aldehyde group and ester group.
The invention also provides a preparation method of the 2-boron alkenyl oxygen ether compound, which comprises the following steps:
dissolving: alkynyl oxygen ether, bisboric acid pinacol ester, PVC loaded nano copper powder balls and alkali are dissolved in an organic solvent;
heating: the dissolution system reacts for a period of time under heating;
purifying: removing the solvent, and separating and purifying to obtain the product.
In order to solve the technical problems, according to one aspect of the present invention, the following technical solutions are provided: the preparation method of the 2-boron alkenyl oxygen ether compound comprises the steps of dissolving alkynyl oxygen ether, bisboronic acid pinacol ester, PVC loaded nanometer copper powder and alkali in a molar ratio of 1:1.0-5.0:0.05-1.0:1.0-5.0.
In order to solve the technical problems, according to one aspect of the present invention, the following technical solutions are provided: the preparation process of 2-boron alkenyl oxygen ether compound includes one or several of methanol, ethanol, tetrahydrofuran, acetonitrile, DMF, dioxane, DMSO and N-methyl pyrrolidone.
In order to solve the technical problems, according to one aspect of the present invention, the following technical solutions are provided: the preparation process of 2-boron alkenyl oxygen ether compound includes the weight-volume ratio of alkynyl oxygen ether to organic solvent of 1g to 50-100 ml.
In order to solve the technical problems, according to one aspect of the present invention, the following technical solutions are provided: a preparation method of a 2-boron alkenyl oxygen ether compound, wherein the heating temperature in heating is 30-180 ℃ and the heating time is 4-72h.
In order to solve the technical problems, according to one aspect of the present invention, the following technical solutions are provided: a preparation method of a 2-boron alkenyl oxygen ether compound, wherein the heating temperature is 60 ℃ and the heating time is 12h.
In order to solve the technical problems, according to one aspect of the present invention, the following technical solutions are provided: a process for preparing 2-boron alkenyl oxygen ether compound includes such steps as removing organic solvent, adding water, stirring for 3-5min, extracting with ethyl acetate, drying organic phase, and column chromatography.
The invention provides a 2-boron alkenyl oxygen ether compound and a preparation method thereof, the obtained product is a 2-boron alkenyl oxygen ether compound, and is also an important organic synthesis intermediate, boron can be further converted into halogenide, alkenyl azide, alkenyl cyanide, alkenyl carboxylic acid and the like, in the preparation process, the boron hydrogenation reaction of alkynyl oxygen ether substrates is realized by taking recyclable PVC loaded nano copper powder balls as catalysts, and the 2-boron alkenyl oxygen ether compound is obtained.
Drawings
FIG. 1 is a nuclear magnetic resonance hydrogen spectrum of the compound cis-1-cyclohexyl-1-pinacol boronate phenyl vinyl ether;
FIG. 2 is a nuclear magnetic resonance carbon spectrum of the compound cis-1-cyclohexyl-1-pinacol boronate phenyl vinyl ether.
Detailed Description
In order that the above-recited objects, features and advantages of the present invention will become more apparent, a more particular description of the invention will be rendered by reference to specific embodiments thereof which are illustrated in the appended drawings.
In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present invention, but the present invention may be practiced in other ways other than those described herein, and persons skilled in the art will readily appreciate that the present invention is not limited to the specific embodiments disclosed below.
Further, reference herein to "one embodiment" or "an embodiment" means that a particular feature, structure, or characteristic can be included in at least one implementation of the invention. The appearances of the phrase "in one embodiment" in various places in the specification are not necessarily all referring to the same embodiment, nor are separate or alternative embodiments mutually exclusive of other embodiments. The following examples are put forth so as to enable those skilled in the art to practice.
The synthesis equation for preparing the 2-boron alkenyl oxygen ether compound is as follows:
the molecular formula of the cis-1-cyclohexyl-1-pinacol boric acid ester phenyl vinyl ether in the prepared product is shown as follows:
the specific sources of the raw materials adopted in the embodiment of the invention are as follows:
cyclohexylacetylene (purity 97%), cyclopropylacetylene (purity 98%), heptyne (purity 99%), phenol (purity 99%), p-cresol (purity 97%), p-ethylphenol (purity 98%), pinacol biborate (purity 98%) were purchased from Shanghai, inc. of medical technology, inc.; PVC (purity: K-value 68-65), sodium methoxide (purity 99%) are purchased from Shanghai Jiding Biotechnology Co., ltd; nanometer copper powder (20-50 nm, purity 98%) was purchased from Shanghai Yi En chemical technology limited company; dioxane (analytically pure), methanol (analytically pure), anhydrous sodium sulfate, ethyl acetate (analytically pure), methylene chloride (analytically pure), petroleum ether (analytically pure), tetrahydrofuran (analytically pure), acetonitrile (analytically pure), DMF (analytically pure), toluene (analytically pure) were purchased from national pharmaceutical chemicals company.
Example 1
20mg (0.1 mmol) of cyclohexyl ethynyl phenoxyether, 25mg (0.10 mmol) of bisboronic acid pinacol ester, 13mg of PVC loaded nano copper powder balls (Cu content is 0.02mmol,1 mg) and 6mg (0.12 mmol) of sodium methoxide are added into a 10mL reaction bottle, 1.5mL of dioxane/methanol (v/v=2/1) is added, the mixture is heated to 60 ℃, the mixture is stirred and reacted for 12h, after the reaction is finished, the mixture is cooled to room temperature, 10mL of ethyl acetate is added, 5mL of water is added for extraction, 10g of anhydrous sodium sulfate is added into an organic phase, the mixture is kept stand and dried for 2h, suction filtration is carried out, the organic solvent is removed by rotary evaporation, 1g of column chromatography silica gel and 5mL of dichloromethane are added into the product, the mixture is uniformly mixed, the solvent is removed by rotary evaporation, a chromatographic column with the length of 30cm and the inner diameter of 3cm is filled into the upper end 5cm of the chromatographic column, and column chromatography is carried out by using petroleum ether/ethyl acetate (50:1) as a mobile phase, so as to obtain oily liquid.
Example 2
20mg (0.1 mmol) of cyclohexyl ethynyl phenoxyether, 38mg (0.15 mmol) of bisboronic acid pinacol ester, 13mg of PVC loaded nano copper powder balls (Cu content is 0.02mmol,1 mg) and 6mg (0.12 mmol) of sodium methoxide are added into a 10mL reaction bottle, 1.5mL of dioxane/methanol (v/v=2/1) is added, the mixture is heated to 60 ℃, the mixture is stirred and reacted for 12h, after the reaction is finished, the mixture is cooled to room temperature, 10mL of ethyl acetate is added, 5mL of water is added for extraction, 10g of anhydrous sodium sulfate is added into an organic phase, the mixture is kept stand and dried for 2h, suction filtration is carried out, the organic solvent is removed by rotary evaporation, 1g of column chromatography silica gel and 5mL of dichloromethane are added into the product, the mixture is uniformly mixed, the solvent is removed by rotary evaporation, a chromatographic column with the length of 30cm and the inner diameter of 3cm is filled into the upper end 5cm of the chromatographic column, and column chromatography is carried out by using petroleum ether/ethyl acetate (50:1) as a mobile phase, so as to obtain oily liquid.
Example 3
20mg (0.1 mmol) of cyclohexyl ethynyl phenoxyether, 76mg (0.3 mmol) of bisboronic acid pinacol ester, 13mg of PVC loaded nano copper powder balls (Cu content is 0.02mmol,1 mg) and 6mg (0.12 mmol) of sodium methoxide are added into a 10mL reaction bottle, 1.5mL of dioxane/methanol (v/v=2/1) is added, the mixture is heated to 60 ℃, the mixture is stirred and reacted for 12h, after the reaction is finished, the mixture is cooled to room temperature, 10mL of ethyl acetate is added, 5mL of water is added for extraction, 10g of anhydrous sodium sulfate is added into an organic phase, the mixture is kept stand and dried for 2h, the solvent is removed by rotary evaporation after the mixture is uniformly mixed, a chromatographic column with 1g of column chromatography silica gel and 5mL of dichloromethane is taken, a chromatographic column with the length of 30cm and the inner diameter of 3cm is filled into the upper end 5cm of the chromatographic column, and column chromatography is carried out by taking petroleum ether/ethyl acetate (50:1) as a mobile phase, so as to obtain oily liquid.
Example 4
20mg (0.1 mmol) of cyclohexyl ethynyl phenoxyether, 38mg (0.15 mmol) of bisboronic acid pinacol ester, 6mg of PVC loaded nano copper powder balls (Cu content is 0.01mmol,0.5 mg) and 6mg (0.12 mmol) of sodium methoxide are added into a 10mL reaction bottle, 1.5mL of dioxane/methanol (v/v=2/1) is added, the mixture is heated to 60 ℃, the mixture is stirred and reacted for 12h, after the reaction is finished, the mixture is cooled to room temperature, 10mL of ethyl acetate is added, 5mL of water is added for extraction, 10g of anhydrous sodium sulfate is added into an organic phase, the mixture is kept stand and dried for 2h, suction filtration is carried out, the organic solvent is removed by rotary evaporation, 1g of column chromatography silica gel and 5mL of dichloromethane are added into the product, the mixture is uniformly mixed, the solvent is removed by rotary evaporation, a chromatographic column with the length of 30cm and the inner diameter of 3cm is filled into the upper end 5cm of the chromatographic column, and column chromatography is carried out by using petroleum ether/ethyl acetate (50:1) as a mobile phase, so as to obtain oily liquid.
Example 5
20mg (0.1 mmol) of cyclohexyl ethynyl phenoxyether, 38mg (0.15 mmol) of bisboronic acid pinacol ester, 19mg of PVC loaded nano copper powder balls (Cu content is 0.03mmol,1.5 mg) and 6mg (0.12 mmol) of sodium methoxide are added into a 10mL reaction bottle, 1.5mL of dioxane/methanol (v/v=2/1) is added, the mixture is heated to 60 ℃, the mixture is stirred and reacted for 12h, after the reaction is finished, the mixture is cooled to room temperature, 10mL of ethyl acetate is added, 5mL of water is added for extraction, 10g of anhydrous sodium sulfate is added into an organic phase, the mixture is kept stand and dried for 2h, suction filtration is carried out, the organic solvent is removed by rotary evaporation, 1g of column chromatography silica gel and 5mL of dichloromethane are added into the product, the mixture is uniformly mixed, the solvent is removed by rotary evaporation, a chromatographic column with the length of 30cm and the inner diameter of 3cm is filled into the upper end 5cm of the chromatographic column, and column chromatography is carried out by using petroleum ether/ethyl acetate (50:1) as a mobile phase, so as to obtain oily liquid.
Example 6
20mg (0.1 mmol) of cyclohexyl ethynyl phenoxyether, 38mg (0.15 mmol) of bisboronic acid pinacol ester, 13mg of PVC loaded nano copper powder balls (Cu content is 0.02mmol,1 mg) and 5mg (0.12 mmol) of sodium hydroxide are added into a 10mL reaction bottle, 1.5mL of dioxane/methanol (v/v=2/1) is added, the mixture is heated to 60 ℃, the mixture is stirred and reacted for 12 hours, after the reaction is finished, the mixture is cooled to room temperature, 10mL of ethyl acetate is added, 5mL of water is added for extraction, 10g of anhydrous sodium sulfate is added into an organic phase, the mixture is kept stand and dried for 2 hours, suction filtration and rotary evaporation are carried out to remove the organic solvent, 1g of column chromatography silica gel and 5mL of dichloromethane are added into the product, the solvent is removed by rotary evaporation after uniform mixing, 30cm long, a 3cm inner diameter chromatographic column is taken, 100-200 meshes of silica gel is filled into the 5cm of the upper end of the chromatographic column, and column chromatography is carried out by taking petroleum ether/ethyl acetate (50:1) as a mobile phase to obtain oily liquid.
Example 7
20mg (0.1 mmol) of cyclohexyl ethynyl phenoxyether, 38mg (0.15 mmol) of bisboronic acid pinacol ester, 13mg of PVC loaded nano copper powder balls (Cu content is 0.02mmol,1 mg) and 14mg (0.12 mmol) of sodium carbonate are added into a 10mL reaction bottle, 1.5mL of dioxane/methanol (v/v=2/1) is added, the mixture is heated to 60 ℃, the mixture is stirred and reacted for 12 hours, after the reaction is finished, the mixture is cooled to room temperature, 10mL of ethyl acetate is added, 5mL of water is added for extraction, 10g of anhydrous sodium sulfate is added into an organic phase, the mixture is kept stand and dried for 2 hours, suction filtration is carried out, the organic solvent is removed by rotary evaporation, 1g of column chromatography silica gel and 5mL of dichloromethane are added into the product, the mixture is uniformly mixed, the solvent is removed by rotary evaporation, a chromatographic column with the length of 30cm and the inner diameter of 3cm is filled into the upper end 5cm of the chromatographic column, and column chromatography is carried out by using petroleum ether/ethyl acetate (50:1) as a mobile phase, so as to obtain oily liquid.
Example 8
20mg (0.1 mmol) of cyclohexyl ethynyl phenoxyether, 38mg (0.15 mmol) of bisboronic acid pinacol ester, 13mg of PVC loaded nano copper powder balls (Cu content is 0.02mmol,1 mg) and 24mg (0.12 mmol) of potassium phosphate are added into a 10mL reaction bottle, 1.5mL of dioxane/methanol (v/v=2/1) is added, the mixture is heated to 60 ℃, the mixture is stirred and reacted for 12 hours, after the reaction is finished, the mixture is cooled to room temperature, 10mL of ethyl acetate is added, 5mL of water is added for extraction, 10g of anhydrous sodium sulfate is added into an organic phase, the mixture is kept stand and dried for 2 hours, suction filtration is carried out, the organic solvent is removed by rotary evaporation, 1g of column chromatography silica gel and 5mL of dichloromethane are added into the product, the mixture is uniformly mixed, the solvent is removed by rotary evaporation, a chromatographic column with the length of 30cm and the inner diameter of 3cm is filled into the upper end 5cm of the chromatographic column, and column chromatography is carried out by using petroleum ether/ethyl acetate (50:1) as a mobile phase, so as to obtain oily liquid.
Example 9
20mg (0.1 mmol) of cyclohexyl ethynyl phenoxyether, 38mg (0.15 mmol) of bisboronic acid pinacol ester, 13mg of PVC loaded nano copper powder balls (Cu content is 0.02mmol,1 mg) and 12mg (0.12 mmol) of triethylamine are added into a 10mL reaction bottle, 1.5mL of dioxane/methanol (v/v=2/1) is added, the mixture is heated to 60 ℃, the mixture is stirred and reacted for 12 hours, after the reaction is finished, the mixture is cooled to room temperature, 10mL of ethyl acetate is added, 5mL of water is added for extraction, 10g of anhydrous sodium sulfate is added into an organic phase, the mixture is kept stand and dried for 2 hours, the solvent is removed by rotary evaporation after the mixture is uniformly mixed, the mixture is subjected to rotary evaporation, a chromatographic column with the length of 30cm and the inner diameter of 3cm is filled into the upper end 5cm of the chromatographic column, and the petroleum ether/ethyl acetate (50:1) is taken as a mobile phase for column chromatography, so as to obtain oily liquid.
Example 10
20mg (0.1 mmol) of cyclohexyl ethynyl phenoxyether, 38mg (0.15 mmol) of bisboronic acid pinacol ester, 13mg of PVC loaded nano copper powder balls (Cu content is 0.02mmol,1 mg) and 6mg (0.12 mmol) of sodium methoxide are added into a 10mL reaction bottle, 1.5mL of methanol is added, the mixture is heated to 60 ℃ and stirred for 12h, after the reaction is finished, the mixture is cooled to room temperature, 10mL of ethyl acetate is added, 5mL of water is added for extraction, 10g of anhydrous sodium sulfate is added into an organic phase, the mixture is left for drying for 2h, suction filtration is carried out, the organic solvent is removed by rotary evaporation, 1g of column chromatography silica gel and 5mL of dichloromethane are added into the product, the solvent is removed by rotary evaporation after the mixture is uniformly mixed, 30cm long, a 3cm inner diameter column is filled at the upper end of the column, and column chromatography is carried out by taking petroleum ether/ethyl acetate (50:1) as a mobile phase.
Example 11
20mg (0.1 mmol) of cyclohexyl ethynyl phenoxyether, 38mg (0.15 mmol) of bisboronic acid pinacol ester, 13mg of PVC loaded nano copper powder balls (Cu content is 0.02mmol,1 mg) and 6mg (0.12 mmol) of sodium methoxide are added into a 10mL reaction bottle, 1.5mL of ethanol is added, the mixture is heated to 60 ℃ and stirred for 12h, after the reaction is finished, the mixture is cooled to room temperature, 10mL of ethyl acetate is added, 5mL of water is added for extraction, 10g of anhydrous sodium sulfate is added into an organic phase, the mixture is left for drying for 2h, suction filtration is carried out, the organic solvent is removed by rotary evaporation, 1g of column chromatography silica gel and 5mL of dichloromethane are added into the product, the solvent is removed by rotary evaporation after the mixture is uniformly mixed, 30cm long, a 3cm inner diameter column is filled at the upper end of the column, and column chromatography is carried out by taking petroleum ether/ethyl acetate (50:1) as a mobile phase.
Example 12
20mg (0.1 mmol) of cyclohexyl ethynyl phenoxyether, 38mg (0.15 mmol) of bisboronic acid pinacol ester, 13mg of PVC loaded nano copper powder balls (Cu content is 0.02mmol,1 mg) and 6mg (0.12 mmol) of sodium methoxide are added into a 10mL reaction bottle, 1.5mL of tetrahydrofuran/methanol (v/v=2/1) is added, the mixture is heated to 60 ℃, the mixture is stirred and reacted for 12 hours, after the reaction is finished, the mixture is cooled to room temperature, 10mL of ethyl acetate is added, 5mL of water is added for extraction, 10g of anhydrous sodium sulfate is added into an organic phase, the mixture is kept stand and dried for 2 hours, suction filtration and rotary evaporation are carried out to remove the organic solvent, 1g of column chromatography silica gel and 5mL of dichloromethane are added into the product, the mixture is uniformly mixed, a 30cm long, a 3cm inner diameter chromatographic column is taken, 100-200 meshes silica gel is filled to the 5cm of the upper end of the chromatographic column, and column chromatography is carried out by taking petroleum ether/ethyl acetate (50:1) as a mobile phase to obtain oily liquid.
Example 12
20mg (0.1 mmol) of cyclohexyl ethynyl phenoxyether, 38mg (0.15 mmol) of bisboronic acid pinacol ester, 13mg of PVC loaded nano copper powder balls (Cu content is 0.02mmol,1 mg) and 6mg (0.12 mmol) of sodium methoxide are added into a 10mL reaction bottle, then 1.5mL of acetonitrile/methanol (v/v=2/1) is added, the mixture is heated to 60 ℃, the mixture is stirred and reacted for 12 hours, after the reaction is finished, the mixture is cooled to room temperature, 10mL of ethyl acetate is added, 5mL of water is added for extraction, 10g of anhydrous sodium sulfate is added into an organic phase, the mixture is left for 2 hours for standing and drying, suction filtration and rotary evaporation are carried out to remove the organic solvent, 1g of column chromatography silica gel and 5mL of dichloromethane are added into the product for uniform mixing, a 30cm long, a 3cm inner diameter chromatographic column is taken, 100-200 meshes of silica gel is filled at the upper end of the chromatographic column, and column chromatography is carried out by taking petroleum ether/ethyl acetate (50:1) as a mobile phase, thus obtaining oily liquid.
Example 13
20mg (0.1 mmol) of cyclohexyl ethynyl phenoxyether, 38mg (0.15 mmol) of bisboronic acid pinacol ester, 13mg of PVC loaded nano copper powder balls (Cu content is 0.02mmol,1 mg) and 6mg (0.12 mmol) of sodium methoxide are added into a 10mL reaction bottle, 1.5mL of toluene/methanol (v/v=2/1) is added, the mixture is heated to 60 ℃, the mixture is stirred and reacted for 12 hours, after the reaction is finished, the mixture is cooled to room temperature, 10mL of ethyl acetate is added, 5mL of water is added for extraction, 10g of anhydrous sodium sulfate is added into an organic phase, the mixture is left for 2 hours for standing and drying, suction filtration and rotary evaporation are carried out to remove the organic solvent, 1g of column chromatography silica gel and 5mL of dichloromethane are added into the product for uniform mixing, a 30cm long, a 3cm inner diameter chromatographic column is taken, 100-200 meshes of silica gel is filled at the upper end of the chromatographic column, and column chromatography is carried out by taking petroleum ether/ethyl acetate (50:1) as a mobile phase, thus obtaining oily liquid.
Example 13
20mg (0.1 mmol) of cyclohexyl ethynyl phenoxyether, 38mg (0.15 mmol) of bisboronic acid pinacol ester, 13mg of PVC loaded nano copper powder balls (Cu content 0.02mmol,1 mg) and 6mg (0.12 mmol) of sodium methoxide are added into a 10mL reaction bottle, 1.5mL of DMF/methanol (v/v=2/1) is added, the mixture is heated to 60 ℃ and stirred for reaction for 12h, after the reaction is finished, the mixture is cooled to room temperature, 10mL of ethyl acetate is added, 5mL of water is added for extraction, 10g of anhydrous sodium sulfate is added into an organic phase, the mixture is left for drying for 2h, suction filtration and rotary evaporation are carried out to remove the organic solvent, 1g of column chromatography silica gel and 5mL of dichloromethane are added into the product for uniform mixing, a 30cm long, a 3cm inner diameter chromatographic column is taken, 100-200 mesh silica gel is filled at the upper end of the chromatographic column, and column chromatography is carried out by taking petroleum ether/ethyl acetate (50:1) as a mobile phase to obtain oily liquid.
Example 14
20mg (0.1 mmol) of cyclohexyl ethynyl phenoxyether, 38mg (0.15 mmol) of bisboronic acid pinacol ester, 13mg of PVC loaded nano copper powder balls (Cu content is 0.02mmol,1 mg) and 6mg (0.12 mmol) of sodium methoxide are added into a 10mL reaction bottle, 1.5mL of toluene/methanol (v/v=2/1) is added, the mixture is heated to 60 ℃, the mixture is stirred and reacted for 12 hours, after the reaction is finished, the mixture is cooled to room temperature, 10mL of ethyl acetate is added, 5mL of water is added for extraction, 10g of anhydrous sodium sulfate is added into an organic phase, the mixture is left for 2 hours for standing and drying, suction filtration and rotary evaporation are carried out to remove the organic solvent, 1g of column chromatography silica gel and 5mL of dichloromethane are added into the product for uniform mixing, a 30cm long, a 3cm inner diameter chromatographic column is taken, 100-200 meshes of silica gel is filled at the upper end of the chromatographic column, and column chromatography is carried out by taking petroleum ether/ethyl acetate (50:1) as a mobile phase, thus obtaining oily liquid.
Example 15
20mg (0.1 mmol) of cyclohexyl ethynyl phenoxyether, 38mg (0.15 mmol) of bisboronic acid pinacol ester, 13mg of PVC loaded nano copper powder balls (Cu content is 0.02mmol,1 mg) and 6mg (0.12 mmol) of sodium methoxide are added into a 10mL reaction bottle, 1.5mL of dioxane/methanol (v/v=2/1) is added, stirring reaction is carried out for 12h at room temperature, 10mL of ethyl acetate is added after the reaction is finished, 5mL of water is added for extraction, 10g of anhydrous sodium sulfate is added into an organic phase, standing and drying are carried out for 2h, suction filtration is carried out, organic solvent is removed by rotary evaporation after 1g of column chromatography silica gel and 5mL of dichloromethane are uniformly mixed, the solvent is removed by rotary evaporation, 30cm long, a chromatographic column with 3cm inner diameter is filled at the upper end of the chromatographic column, column chromatography is carried out by taking petroleum ether/ethyl acetate (50:1) as a mobile phase, and oily liquid is obtained by column chromatography.
Example 16
20mg (0.1 mmol) of cyclohexyl ethynyl phenoxyether, 38mg (0.15 mmol) of bisboronic acid pinacol ester, 13mg of PVC loaded nano copper powder balls (Cu content is 0.02mmol,1 mg) and 6mg (0.12 mmol) of sodium methoxide are added into a 10mL reaction bottle, 1.5mL of toluene/methanol (v/v=2/1) is added, heating is carried out to 90 ℃, stirring is carried out for 12h, cooling to room temperature after the reaction is finished, 10mL of ethyl acetate is added, 5mL of water is added for extraction, 10g of anhydrous sodium sulfate is added into an organic phase, standing and drying are carried out for 2h, suction filtration is carried out, the organic solvent is removed by rotary evaporation, 1g of column chromatography silica gel and 5mL of dichloromethane are added into the product, the solvent is removed by rotary evaporation after the mixture is uniform, a chromatographic column with the length of 30cm and the inner diameter of 3cm is filled into the upper end 5cm of the chromatographic column, and column chromatography is carried out by taking petroleum ether/ethyl acetate (50:1) as a mobile phase, thus oily liquid is obtained.
Example 17
20mg (0.1 mmol) of cyclohexyl ethynyl phenoxyether, 38mg (0.15 mmol) of bisboronic acid pinacol ester, 13mg of PVC loaded nano copper powder balls (Cu content is 0.02mmol,1 mg) and 6mg (0.12 mmol) of sodium methoxide are added into a 10mL reaction bottle, 1.5mL of toluene/methanol (v/v=2/1) is added, the mixture is heated to 60 ℃ and stirred for 2h, after the reaction is finished, the mixture is cooled to room temperature, 10mL of ethyl acetate is added, 5mL of water is added for extraction, 10g of anhydrous sodium sulfate is added into an organic phase, the mixture is left for 2h of standing and drying, suction filtration and rotary evaporation are carried out to remove the organic solvent, 1g of column chromatography silica gel and 5mL of dichloromethane are added into the product, the solvent is removed by rotary evaporation after the mixture is uniformly mixed, a column chromatography column with the length of 30cm and the inner diameter of 3cm is filled at the upper end of the column chromatography of 100-200 meshes, and the petroleum ether/ethyl acetate (50:1) is taken as a mobile phase for column chromatography to obtain oily liquid.
Example 18
20mg (0.1 mmol) of cyclohexyl ethynyl phenoxyether, 38mg (0.15 mmol) of bisboronic acid pinacol ester, 13mg of PVC loaded nano copper powder balls (Cu content is 0.02mmol,1 mg) and 6mg (0.12 mmol) of sodium methoxide are added into a 10mL reaction bottle, 1.5mL of toluene/methanol (v/v=2/1) is added, the mixture is heated to 60 ℃ and stirred for reaction for 72h, after the reaction is finished, the mixture is cooled to room temperature, 10mL of ethyl acetate is added, 5mL of water is added for extraction, 10g of anhydrous sodium sulfate is added into an organic phase, the mixture is left for drying for 2h, suction filtration and rotary evaporation are carried out to remove the organic solvent, 1g of column chromatography silica gel and 5mL of dichloromethane are added into the product for uniform mixing, a 30cm long, a 3cm inner diameter chromatographic column is taken, 100-200 mesh silica gel is filled at the upper end of the chromatographic column, and column chromatography is carried out by taking petroleum ether/ethyl acetate (50:1) as a mobile phase to obtain oily liquid.
Example 19
Taking 17mg (0.1 mmol) of cyclopropynyl p-tolueneoxy ether, 38mg (0.15 mmol) of bisboronic acid pinacol ester, 13mg (Cu content is 0.02mmol,1 mg) of PVC loaded nano copper powder balls and 6mg (0.12 mmol) of sodium methoxide, adding 1.5mL of toluene/methanol (v/v=2/1) into a 10mL reaction bottle, heating to 60 ℃, stirring for reaction for 12h, cooling to room temperature after the reaction is finished, adding 10mL of ethyl acetate, adding 5mL of water for extraction, adding 10g of anhydrous sodium sulfate into an organic phase, standing for drying for 2h, filtering, rotationally evaporating to remove the organic solvent, adding 1g of column chromatography silica gel and 5mL of dichloromethane into the product, uniformly mixing, rotationally evaporating to remove the solvent, taking a chromatographic column with the length of 30cm, filling the chromatographic column with the inner diameter of 3cm to the position of 5cm at the upper end of the chromatographic column, and carrying out column chromatography by taking petroleum ether/ethyl acetate (50:1) as a mobile phase to obtain oily liquid.
Example 20
20mg (0.1 mmol) of heptynyl p-tolueneoxy ether, 38mg (0.15 mmol) of bisboronic acid pinacol ester, 13mg (Cu content 0.02mmol,1 mg) of PVC-loaded nano copper powder balls and 6mg (0.12 mmol) of sodium methoxide are taken and added into a 10mL reaction bottle, 1.5mL of toluene/methanol (v/v=2/1) is added, the mixture is heated to 60 ℃ and stirred for reaction for 12h, after the reaction is finished, the mixture is cooled to room temperature, 10mL of ethyl acetate is added, 5mL of water is added for extraction, 10g of anhydrous sodium sulfate is added into an organic phase, the mixture is left for drying for 2h, suction filtration and rotary evaporation are carried out to remove the organic solvent, 1g of column chromatography silica gel and 5mL of dichloromethane are added into the product for uniform mixing, a 30cm long, a 3cm inner diameter chromatographic column is taken, 100-200 mesh silica gel is filled at the upper end of the chromatographic column, and column chromatography is carried out by taking petroleum ether/ethyl acetate (50:1) as a mobile phase to obtain oily liquid.
Example 21
Taking 22mg (0.1 mmol) of heptynyl p-ethylbenzene oxyether, 38mg (0.15 mmol) of bisboronic acid pinacol ester, 13mg of PVC-loaded nano copper powder balls (Cu content is 0.02mmol,1 mg) and 6mg (0.12 mmol) of sodium methoxide, adding 1.5mL of toluene/methanol (v/v=2/1) into a 10mL reaction bottle, heating to 60 ℃, stirring for reaction for 12h, cooling to room temperature after the reaction is finished, adding 10mL of ethyl acetate, adding 5mL of water for extraction, adding 10g of anhydrous sodium sulfate into an organic phase, standing for drying for 2h, filtering, rotationally evaporating to remove the organic solvent, adding 1g of column chromatography silica gel and 5mL of dichloromethane into the product, uniformly mixing, rotationally evaporating to remove the solvent, taking a chromatographic column with the length of 30cm and the inner diameter of 3cm, filling the silica gel with the size of 100-200 meshes to the upper end of the chromatographic column, and carrying out column chromatography by taking petroleum ether/ethyl acetate (50:1) as a mobile phase to obtain oily liquid.
Example 22
The oily liquids obtained by column chromatography in examples 1 to 21 were weighed to obtain the weight of the product, which was compared with the weight of the raw materials charged into the reaction, and the weight of the product was calculated from the weight of the product and the weight of the raw materials, and the yield was calculated as follows:
and simultaneously, nuclear magnetic resonance detection is carried out on the products, and the types of the products in the examples 1-21 are clear according to a hydrogen spectrum and a carbon spectrum decomposition spectrum.
The product types and yields data obtained are recorded in table 1.
TABLE 1 kinds and yields of products prepared in examples 1 to 21
According to Table 1, the yields of the products according to examples 1-3 are obtained, the yields of example 2 in examples 1-3 are highest, the yields are best when the amount of the bisboronic acid pinacol ester is 1.5 times that of the alkyne, the yields of the products according to examples 2, 4-5 are obtained, the yields of example 2 are highest, and the yields are highest when the amount of the copper catalyst is 20%; the yield data for the products of examples 2, 6-9 are available, with example 2 having the highest yield when sodium methoxide is used as base; the yields of the products according to examples 2, 10 to 14 were obtained, with example 2 being the highest yield, using dioxane/methanol as solvent; according to the yield data of the products in examples 2, 15 to 16, the yield of example 2 is highest, the yield is highest when the heating temperature is set at 60 ℃, and the heating temperature is set at 60 ℃ as a preferable heating temperature; according to the yield data of the products in examples 2, 17 to 18, the yield of example 2 was highest, and the reaction time was set at 12 hours, with the highest yield obtained and the reaction time of 1 being the preferred reaction time setting.
The images of the products obtained in examples 1 to 18 on the nmr hydrogen spectrum and nmr carbon spectrum are identical to those shown in fig. 1 and 2.
The nuclear magnetic resonance hydrogen spectrum data are: 1 H NMR(400MHz,CDCl 3 )δ7.34(t,J＝7.9Hz,2H),7.10(t,J＝8.2Hz,3H),6.97(s,1H),2.73-2.65(m,1H),1.82–1.55(m,10H),1.28(s,12H).
the nuclear magnetic resonance carbon spectrum data are: 13 C NMR(101MHz,CDCl 3 )δ157.42,150.70,129.54,123.12,117.37,82.64,35.95,32.00,26.91,26.18,24.73.
according to the drawings and the resolution, the products prepared in examples 1 to 18 are the same, and are cis-1-cyclohexyl-1-pinacol boric acid ester-based phenyl vinyl ether.
According to the data of examples 1 to 21, the synthetic route provided by the invention has the synthetic capability for various 2-boron-based alkenyl oxygen ether compounds, and simultaneously has the capability of synthesizing the same target 2-boron-based alkenyl oxygen ether compound by using various raw materials, and by the conclusion, the synthetic route provided by the invention is a synthetic method of the 2-boron-based alkenyl oxygen ether compound, which can be applied to the synthesis of various 2-boron-based alkenyl oxygen ether compounds and the synthesis of various raw materials, compared with the current synthetic method of the compound, the synthetic route provided by the invention has the advantages of wide substrate application range and various target product types, and the application range of the technical scheme in actual production is enlarged.
The preparation method of the target compound has the advantages of simple process, simple and convenient steps, shorter reaction time than the conventional compound synthesis method, milder reaction conditions, simple subsequent treatment and suitability for mass production.
It should be noted that the above embodiments are only for illustrating the technical solution of the present invention and not for limiting the same, and although the present invention has been described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that the technical solution of the present invention may be modified or substituted without departing from the spirit and scope of the technical solution of the present invention, which is intended to be covered in the scope of the claims of the present invention.
Claims (1)
1. A preparation method of a 2-boron alkenyl oxygen ether compound is characterized by comprising the following steps: the method comprises the following steps: comprising the steps of (a) a step of,
adding 20mg of cyclohexyl ethynyl phenoxyether, 38mg of bisboronic acid pinacol ester, 13mg of PVC loaded nano copper powder balls and 6mg of sodium methoxide into a 10mL reaction bottle, adding 1.5mL of dioxane/methanol, heating to 60 ℃, stirring for reacting for 12 hours, cooling to room temperature after the reaction is finished, adding 10mL of ethyl acetate, adding 5mL of water for extraction, adding 10g of anhydrous sodium sulfate into an organic phase, standing for drying for 2 hours, filtering, rotationally evaporating to remove the organic solvent, adding 1g of column chromatography silica gel and 5mL of dichloromethane into the product, uniformly mixing, rotationally evaporating to remove the solvent, taking a chromatographic column with the length of 30cm and the inner diameter of 3cm, filling 100-200 meshes of silica gel into the 5cm position at the upper end of the chromatographic column, and carrying out column chromatography by taking petroleum ether/ethyl acetate as a mobile phase to obtain oily liquid;
wherein, the Cu content in the PVC loaded nano copper powder sphere is 0.02mmol and 1mg;
the volume ratio of the dioxane to the methanol is 2:1;
the volume ratio of petroleum ether to ethyl acetate is 50:1.
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