CN114315885B - Method for catalytic synthesis of methyl 3-hydroxy-4- ((trimethylsilyl) ethynyl) benzoate - Google Patents
Method for catalytic synthesis of methyl 3-hydroxy-4- ((trimethylsilyl) ethynyl) benzoate Download PDFInfo
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- 238000000034 method Methods 0.000 title claims abstract description 30
- IGKWQEJDFVUAME-UHFFFAOYSA-N methyl 3-hydroxy-4-(2-trimethylsilylethynyl)benzoate Chemical compound COC(=O)C1=CC=C(C#C[Si](C)(C)C)C(O)=C1 IGKWQEJDFVUAME-UHFFFAOYSA-N 0.000 title claims abstract description 20
- 238000007036 catalytic synthesis reaction Methods 0.000 title claims abstract description 15
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 claims abstract description 156
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims abstract description 92
- 239000003054 catalyst Substances 0.000 claims abstract description 84
- 239000004408 titanium dioxide Substances 0.000 claims abstract description 78
- 229910052763 palladium Inorganic materials 0.000 claims abstract description 46
- 239000004005 microsphere Substances 0.000 claims abstract description 34
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 claims abstract description 24
- -1 (trimethylsilyl) ethynyl Chemical group 0.000 claims abstract description 15
- 229940095102 methyl benzoate Drugs 0.000 claims abstract description 12
- CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 claims abstract description 11
- 230000002194 synthesizing effect Effects 0.000 claims abstract description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 39
- 238000006243 chemical reaction Methods 0.000 claims description 36
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 28
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 27
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 25
- 238000005406 washing Methods 0.000 claims description 24
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 21
- VXUYXOFXAQZZMF-UHFFFAOYSA-N titanium(IV) isopropoxide Chemical compound CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C VXUYXOFXAQZZMF-UHFFFAOYSA-N 0.000 claims description 20
- 239000003960 organic solvent Substances 0.000 claims description 19
- 238000003756 stirring Methods 0.000 claims description 19
- FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 claims description 18
- 239000002243 precursor Substances 0.000 claims description 17
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 16
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 15
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 15
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 14
- 239000002105 nanoparticle Substances 0.000 claims description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 12
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 12
- 238000001027 hydrothermal synthesis Methods 0.000 claims description 12
- 239000002253 acid Substances 0.000 claims description 11
- 238000001914 filtration Methods 0.000 claims description 11
- 239000012043 crude product Substances 0.000 claims description 10
- 239000007788 liquid Substances 0.000 claims description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 10
- 229910021595 Copper(I) iodide Inorganic materials 0.000 claims description 9
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 9
- 230000032683 aging Effects 0.000 claims description 9
- 239000003513 alkali Substances 0.000 claims description 9
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 claims description 9
- LXCQVWRESZDFGW-UHFFFAOYSA-N methyl 3-hydroxy-4-iodobenzoate Chemical compound COC(=O)C1=CC=C(I)C(O)=C1 LXCQVWRESZDFGW-UHFFFAOYSA-N 0.000 claims description 9
- 239000004323 potassium nitrate Substances 0.000 claims description 9
- 235000010333 potassium nitrate Nutrition 0.000 claims description 9
- 238000002360 preparation method Methods 0.000 claims description 9
- 239000008367 deionised water Substances 0.000 claims description 8
- 229910021641 deionized water Inorganic materials 0.000 claims description 8
- 238000002156 mixing Methods 0.000 claims description 8
- 239000012074 organic phase Substances 0.000 claims description 8
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 claims description 8
- 239000012071 phase Substances 0.000 claims description 8
- 238000010992 reflux Methods 0.000 claims description 8
- 238000000926 separation method Methods 0.000 claims description 8
- 238000001354 calcination Methods 0.000 claims description 7
- 238000011068 loading method Methods 0.000 claims description 7
- 239000002904 solvent Substances 0.000 claims description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 6
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 5
- 230000003213 activating effect Effects 0.000 claims description 5
- 238000004128 high performance liquid chromatography Methods 0.000 claims description 5
- 238000012544 monitoring process Methods 0.000 claims description 5
- 239000002244 precipitate Substances 0.000 claims description 5
- 238000004064 recycling Methods 0.000 claims description 5
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 claims description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- 235000019441 ethanol Nutrition 0.000 claims description 4
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 4
- 239000002994 raw material Substances 0.000 claims description 4
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 3
- 229910017604 nitric acid Inorganic materials 0.000 claims description 3
- 230000035484 reaction time Effects 0.000 claims description 3
- VSTXCZGEEVFJES-UHFFFAOYSA-N 1-cycloundecyl-1,5-diazacycloundec-5-ene Chemical compound C1CCCCCC(CCCC1)N1CCCCCC=NCCC1 VSTXCZGEEVFJES-UHFFFAOYSA-N 0.000 claims description 2
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 claims description 2
- 238000003483 aging Methods 0.000 claims description 2
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 claims description 2
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 claims description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
- 238000006467 substitution reaction Methods 0.000 claims description 2
- 230000015572 biosynthetic process Effects 0.000 abstract description 7
- 238000003786 synthesis reaction Methods 0.000 abstract description 7
- 239000000463 material Substances 0.000 abstract description 6
- 230000008929 regeneration Effects 0.000 abstract description 5
- 238000011069 regeneration method Methods 0.000 abstract description 5
- 238000006555 catalytic reaction Methods 0.000 abstract description 3
- 230000000694 effects Effects 0.000 abstract description 2
- 238000011084 recovery Methods 0.000 abstract description 2
- 239000000047 product Substances 0.000 description 16
- 238000005119 centrifugation Methods 0.000 description 10
- 238000001035 drying Methods 0.000 description 10
- 230000003197 catalytic effect Effects 0.000 description 8
- 239000000203 mixture Substances 0.000 description 7
- 238000004821 distillation Methods 0.000 description 6
- 239000002077 nanosphere Substances 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 229910052739 hydrogen Inorganic materials 0.000 description 5
- 230000001133 acceleration Effects 0.000 description 4
- 230000005540 biological transmission Effects 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 238000000227 grinding Methods 0.000 description 3
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 3
- 239000004810 polytetrafluoroethylene Substances 0.000 description 3
- 239000008213 purified water Substances 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 230000001172 regenerating effect Effects 0.000 description 3
- 238000007789 sealing Methods 0.000 description 3
- 238000001308 synthesis method Methods 0.000 description 3
- RVDHGRQELZPGCO-UHFFFAOYSA-N 1-benzofuran-6-carboxylic acid Chemical compound OC(=O)C1=CC=C2C=COC2=C1 RVDHGRQELZPGCO-UHFFFAOYSA-N 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 239000012876 carrier material Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000007797 corrosion Effects 0.000 description 2
- 238000005260 corrosion Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000002086 nanomaterial Substances 0.000 description 2
- JKDRQYIYVJVOPF-FDGPNNRMSA-L palladium(ii) acetylacetonate Chemical compound [Pd+2].C\C([O-])=C\C(C)=O.C\C([O-])=C\C(C)=O JKDRQYIYVJVOPF-FDGPNNRMSA-L 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000004627 transmission electron microscopy Methods 0.000 description 2
- KXGFMDJXCMQABM-UHFFFAOYSA-N 2-methoxy-6-methylphenol Chemical compound [CH]OC1=CC=CC([CH])=C1O KXGFMDJXCMQABM-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 208000003556 Dry Eye Syndromes Diseases 0.000 description 1
- 206010013774 Dry eye Diseases 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- YHWCPXVTRSHPNY-UHFFFAOYSA-N butan-1-olate;titanium(4+) Chemical compound [Ti+4].CCCC[O-].CCCC[O-].CCCC[O-].CCCC[O-] YHWCPXVTRSHPNY-UHFFFAOYSA-N 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 238000003763 carbonization Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- YNHIGQDRGKUECZ-UHFFFAOYSA-N dichloropalladium;triphenylphosphanium Chemical compound Cl[Pd]Cl.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-N 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- JFOZKMSJYSPYLN-QHCPKHFHSA-N lifitegrast Chemical compound CS(=O)(=O)C1=CC=CC(C[C@H](NC(=O)C=2C(=C3CCN(CC3=CC=2Cl)C(=O)C=2C=C3OC=CC3=CC=2)Cl)C(O)=O)=C1 JFOZKMSJYSPYLN-QHCPKHFHSA-N 0.000 description 1
- 229960005381 lifitegrast Drugs 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 238000001000 micrograph Methods 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 239000012450 pharmaceutical intermediate Substances 0.000 description 1
- 239000005011 phenolic resin Substances 0.000 description 1
- 229920001568 phenolic resin Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 238000002791 soaking Methods 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 229920000428 triblock copolymer Polymers 0.000 description 1
- VFFKJOXNCSJSAQ-UHFFFAOYSA-N trimethylsilyl benzoate Chemical compound C[Si](C)(C)OC(=O)C1=CC=CC=C1 VFFKJOXNCSJSAQ-UHFFFAOYSA-N 0.000 description 1
- POXSDSRWVJZWCN-UHFFFAOYSA-N triphenylphosphanium;iodide Chemical compound I.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 POXSDSRWVJZWCN-UHFFFAOYSA-N 0.000 description 1
- 238000009461 vacuum packaging Methods 0.000 description 1
Abstract
The invention relates to a method for synthesizing methyl 3-hydroxy-4- ((trimethylsilyl) ethynyl) benzoate by catalysis, belonging to the technical fields of medical intermediate synthesis and material synthesis. Under the action of a palladium-loaded titanium dioxide hollow nano microsphere catalyst, 4-iodo-3-hydroxy methyl benzoate and trimethylsilyl acetylene react to generate 3-hydroxy-4- ((trimethylsilyl) ethynyl) methyl benzoate. The catalyst prepared by the invention has simple synthesis, easy recovery and good regeneration effect. And the catalytic synthesis method of the 3-hydroxy-4- ((trimethylsilyl) ethynyl) methyl benzoate is simple, the operation is easy, the yield can reach 95%, and the obtained product has stable quality and higher purity.
Description
Technical Field
The invention relates to a method for synthesizing methyl 3-hydroxy-4- ((trimethylsilyl) ethynyl) benzoate by catalysis, belonging to the technical fields of medical intermediate synthesis and material synthesis.
Background
Methyl 3-hydroxy-4- ((trimethylsilyl) ethynyl) benzoate is an important pharmaceutical intermediate, mainly for the synthesis of the key fragment benzofuran-6-carboxylic acid of betahist. Litaset is the first new drug that can be used to improve and treat dry eye. Therefore, the demand of methyl 3-hydroxy-4- ((trimethylsilyl) ethynyl) benzoate will increase over time, and the market prospect is quite broad.
The catalytic technology using nano material as catalyst provides an effective way for catalyzing synthetic reaction, treating environmental pollution and other aspects. Titanium dioxide is one of the most common nano materials, and has many advantages such as simple preparation process, low manufacturing cost, higher catalytic activity than the conventional catalyst, stable chemical property, acid and alkali corrosion resistance, chemical corrosion resistance, no toxicity and the like, so the titanium dioxide has more researches. The catalyst prepared by taking titanium dioxide as a catalyst carrier and loading corresponding metal ions can remarkably improve the catalytic performance of the catalyst. In addition, the titanium dioxide carrier has high mechanical strength, can reduce mechanical damage as much as possible, and has good regeneration function.
Chinese patent CN108906134A discloses a titanium dioxide material, a preparation method thereof and a supported palladium catalyst, according to weight parts, 5-6 parts of boric acid is dissolved in 10-11 parts of absolute ethyl alcohol, 10-11 parts of tetrabutyl titanate is added into the solution, and the solution is placed in a high-pressure reaction kettle to react for 23-25 hours at 175-185 ℃; performing solid-liquid separation to obtain a white prefabricated material, boiling the white prefabricated material in 100-300 parts of boiling water for 1-2 hours, performing solid-liquid separation, and drying to obtain a titanium dioxide material; mixing titanium dioxide carrier material with the mass ratio of 35:1-350:1 with palladium acetylacetonate, heating under nitrogen and then hydrogen atmosphere, and cooling to obtain the supported palladium catalyst. The process of the catalyst is relatively complex, and in the loading process, the mixture of the titanium dioxide carrier material and palladium acetylacetonate is heated for 4-5 hours at 118-122 ℃ under the nitrogen atmosphere, and then the atmosphere is switched into hydrogen, so that the preparation conditions are relatively harsh.
Chinese patent CN112625057a discloses a method for synthesizing methyl 3-hydroxy-4- ((trimethylsilyl) ethynyl) benzoate, which uses methyl 4-iodo-3-hydroxybenzoate and trimethylsilylacetylene as raw materials, and uses palladium-supported ordered mesoporous carbon catalyst and cuprous iodide-triphenylphosphine complex to catalyze and synthesize methyl 3-hydroxy-4- ((trimethylsilyl) benzoate in an alkaline system. The patent uses A-order phenolic resin as a carbon source, uses triblock copolymer as a template agent, and synthesizes an ordered mesoporous carbon catalyst carrier after high-temperature carbonization; and loading palladium on the ordered mesoporous carbon catalyst carrier to obtain the palladium-loaded ordered mesoporous carbon catalyst. In the preparation process of the catalyst, the template agent is required to be used for correcting the catalyst form, and the preparation process of the catalyst carrier is complex.
In the current synthesis method of 3-hydroxy-4- ((trimethylsilyl) ethynyl) methyl benzoate, bis (triphenylphosphine) palladium dichloride is basically used as a catalyst. However, the catalyst has the advantages of high price, low catalytic efficiency, low recycling rate and difficult recycling. And thus the production cost of the product is too high.
Disclosure of Invention
Aiming at the defects of the prior art, the invention aims to provide a method for synthesizing 3-hydroxy-4- ((trimethylsilyl) ethynyl) methyl benzoate by catalysis, wherein the preparation method of the palladium-supported titanium dioxide hollow nano microsphere catalyst is relatively simple, the catalytic efficiency of the catalyst is high, the reaction time is shortened, and the catalyst is easy to recycle and regenerate after the reaction; and the catalytic efficiency is still higher after regeneration.
The invention relates to a method for catalytic synthesis of methyl 3-hydroxy-4- ((trimethylsilyl) ethynyl) benzoate, which comprises the following steps: under the action of a palladium-loaded titanium dioxide hollow nano microsphere catalyst, 4-iodo-3-hydroxy methyl benzoate reacts with trimethylsilylacetylene to generate 3-hydroxy-4- ((trimethylsilyl) ethynyl) methyl benzoate; the palladium-loaded titanium dioxide hollow nanoparticle catalyst is prepared by taking tetraisopropyl titanate as a raw material, synthesizing a titanium dioxide precursor by an aging method, preparing the titanium dioxide hollow nanoparticle by a hydrothermal method, and finally loading palladium on the titanium dioxide hollow nanoparticle.
Wherein:
The palladium loading amount in the palladium loaded titanium dioxide hollow nano microsphere catalyst is 0.05-1.5% of the mass of the catalyst carrier; the mass of the palladium-loaded titanium dioxide hollow nano microsphere catalyst is 1.5-3.5% of the mass of the 4-iodine-3-hydroxybenzoic acid methyl ester.
The preparation method of the palladium-loaded titanium dioxide hollow nanoparticle catalyst comprises the following steps:
(1) The potassium nitrate solution is transferred into an organic solvent to be fully mixed, then tetraisopropyl titanate is added, and a titanium dioxide precursor is obtained through stirring, ageing and centrifugation;
(2) Adding titanium dioxide precursor into hydrogen peroxide, adding alkali, mixing, performing hydrothermal reaction, centrifuging after the reaction is finished to obtain precipitate, washing, transferring into acid liquor, centrifuging, washing, and calcining to obtain titanium dioxide hollow nano microspheres;
(3) The hollow titanium dioxide microsphere reacts with palladium dichloride to obtain the palladium-loaded hollow titanium dioxide microsphere catalyst.
Wherein the method comprises the steps of
In the step (1), the concentration of the potassium nitrate solution is 0.05-1.15mol/L, the organic solvent is one or more of absolute ethyl alcohol, methanol, isopropanol or toluene, the aging time is 12-48 hours, and the volume and use ratio of the potassium nitrate solution to the tetraisopropyl titanate is 0.15-0.75:6.
In the step (2), the concentration of the hydrogen peroxide is 0.01-0.35wt.%; the alkali is one or more of sodium hydroxide, potassium hydroxide or aluminum hydroxide; the hydrothermal reaction temperature is 120-300 ℃, and the hydrothermal reaction time is 1-6 hours; the calcination temperature is 250-800 ℃; the washing solvent is one or more of absolute ethyl alcohol, methanol, toluene, acetone or methyl tertiary butyl ether; the dosage ratio of hydrogen peroxide to titanium dioxide precursor to alkali is as follows: 40-45:0.2:0.35-0.55, wherein the hydrogen peroxide is calculated by ml, and the titanium dioxide precursor and the alkali are calculated by g.
In the step (3), the reaction system of the titanium dioxide hollow nano-microspheres and palladium dichloride is one or more of deionized water, methanol, ethanol or ethyl acetate; the mass ratio of the titanium dioxide hollow nano-microsphere to the palladium dichloride is 1:0.08-0.15.
The invention relates to a method for catalytic synthesis of methyl 3-hydroxy-4- ((trimethylsilyl) ethynyl) benzoate, which specifically comprises the following steps:
(1) Mixing an organic solvent, 4-iodine-3-hydroxybenzoic acid methyl ester, an alkaline solvent, cuprous iodide and triphenylphosphine, performing nitrogen substitution, adding a palladium-loaded titanium dioxide hollow nanoparticle catalyst, controlling the temperature of a reaction system, dropwise adding trimethylsilylacetylene, keeping the temperature for reaction after the dropwise addition is finished, and monitoring the end point of the reaction by HPLC;
(2) Adding the reaction solution after the reaction into water, dropwise adding acid liquor, adjusting the pH value of the system to be strong acid, standing, separating the solution, and distilling the organic phase to obtain a crude product; adding an organic solvent into the crude product, and distilling to obtain 3-hydroxy-4- ((trimethylsilyl) ethynyl) methyl benzoate;
(3) And filtering the water phase obtained by liquid separation to obtain the palladium-loaded titanium dioxide hollow nano microsphere catalyst, washing by an organic solvent, activating and recycling.
Wherein:
In the step (1), the organic solvent is one or more of toluene, dichloromethane or chloroform; the alkaline solvent is one or more of triethylamine, diethylamine, tetramethyl ethylenediamine and 1, 8-diazabicyclo undec-7-ene; the mass of the cuprous iodide is 4-9% of the mass of the 4-iodo-3-hydroxybenzoic acid methyl ester, the mass of the triphenylphosphine is 45-75% of the mass of the cuprous iodide, and the mass ratio of the trimethylsilylacetylene to the 4-iodo-3-hydroxybenzoic acid methyl ester is 1.20-1.40:3; the mass ratio of the organic solvent to the methyl 4-iodo-3-hydroxybenzoate to the alkaline solvent is 12:1:1.05-1.30.
In the step (2), the acid liquor is one or more of 6-8M hydrochloric acid, 2-3M sulfuric acid or 4-6M nitric acid, the strong acid pH value range is 0.5-3.3, and the organic solvent is one or more of methanol, ethanol, isopropanol, acetone, butanone or toluene.
In the step (3), the organic solvent is one or more of methanol, absolute ethyl alcohol, isopropanol, acetone, methyl tertiary butyl ether, diethyl ether, n-heptane or n-hexane; the washing adopts reflux washing, and the reflux washing time is 4-9 hours.
The methyl 3-hydroxy-4- ((trimethylsilyl) ethynyl) benzoate disclosed by the invention is an intermediate of benzofuran-6-carboxylic acid in LIFITEGRAST key fragments. The synthetic route is as follows:
The beneficial effects of the invention are as follows:
(1) The palladium-loaded titanium dioxide hollow nanoparticle catalyst synthesized by the method has the advantages of simple synthesis method and obvious catalytic effect.
(2) The synthesis method of the 3-hydroxy-4- ((trimethylsilyl) ethynyl) methyl benzoate has simple process and easy operation, and the total reaction mass yield is more than 95%.
(3) The palladium-loaded titanium dioxide hollow nanoparticle catalyst synthesized by the invention can shorten the process time for synthesizing 3-hydroxy-4- ((trimethylsilyl) ethynyl) methyl benzoate.
(4) The palladium-loaded titanium dioxide hollow nanoparticle catalyst synthesized by the method is easy to recycle, is simple to use after recycling, and can be regenerated after reflux washing of an organic solvent.
(5) The palladium-loaded titanium dioxide hollow nano microsphere catalyst synthesized by the method has higher catalytic capability after regeneration.
In conclusion, the invention takes tetraisopropyl titanate as a raw material, synthesizes a titanium dioxide precursor in a nearly neutral organic solvent system, then prepares titanium dioxide hollow nano-microspheres by adopting a hydrothermal method, and obtains the palladium-loaded titanium dioxide hollow nano-microsphere catalyst after palladium metal is loaded. The invention utilizes palladium-loaded titanium dioxide hollow nano microsphere catalyst to catalyze and synthesize 3-hydroxy-4- ((trimethylsilyl) ethynyl) methyl benzoate. The catalyst prepared by the invention has simple synthesis, easy recovery and good regeneration effect. And the catalytic synthesis method of the 3-hydroxy-4- ((trimethylsilyl) ethynyl) methyl benzoate is simple and easy to operate, the yield can reach 95%, the quality of the obtained product is stable, and the purity of the product is still more than 98% after 15 days of acceleration experiments are found through the stability acceleration experiments.
Drawings
FIG. 1 is a transmission electron microscope image of the catalyst of example 1;
FIG. 2 is a transmission electron microscopy image of the catalyst of example 2;
FIG. 3 is a transmission electron microscopy image of the catalyst of example 3;
FIG. 4 is a chromatogram of the product obtained in example 1;
FIG. 5 is a chromatogram of the product obtained in example 2;
FIG. 6 is a chromatogram of the product obtained in example 3.
Detailed Description
The invention will be further illustrated with reference to specific examples.
Example 1
(1) 30Ml of absolute ethyl alcohol was added to a 50ml three-necked round bottom flask, 0.5ml of potassium nitrate solution (0.1 mol/L) was added dropwise thereto, and the mixture was stirred well, 6ml of tetraisopropyl titanate was added thereto, and stirring vigorously was carried out until white precipitate appeared. And (5) after sealing, standing and aging for 24 hours. And (3) after centrifugation and washing with purified water, drying at 60 ℃ to obtain the titanium dioxide precursor. Placing 0.2g of titanium dioxide precursor in a beaker, adding 40ml of 0.05wt.% H 2O2 solution, fully stirring, adding 0.4g of sodium hydroxide solid, placing the mixture in a hydrothermal kettle with a polytetrafluoroethylene lining, and carrying out hydrothermal reaction for 3 hours at 180 ℃; the resulting reaction was washed with centrifugation and absolute ethanol. Adding 20ml of hydrochloric acid (0.1 mol/L) into the washed sample, soaking for 10 minutes, and washing with centrifugation, absolute ethyl alcohol and deionized water to obtain a sample; drying the sample at 60 ℃, grinding, and calcining at 350 ℃ for 5 hours to obtain the catalyst carrier titanium dioxide hollow nano-microsphere.
Adding 1g of titanium dioxide hollow nanospheres serving as a catalyst carrier into 30ml of deionized water, adding 0.1g of palladium dichloride, stirring for 3 hours at normal temperature, filtering, and drying the solid obtained by filtering at 60 ℃ to obtain the palladium-loaded titanium dioxide hollow nanospheres, wherein the load of palladium is 0.76% of the mass of the catalyst carrier. The transmission electron microscope diagram of the catalyst is shown in figure 1.
(2) 36G of dichloromethane, 3g of 4-iodo-3-hydroxybenzoic acid methyl ester, 3.3g of triethylamine, 0.16g of cuprous iodide and 0.088g of triphenylphosphine are added into a 100ml reaction bottle, and after nitrogen replacement, 0.048g of palladium-loaded titanium dioxide hollow microsphere catalyst is added; controlling the temperature in the reaction kettle to be 20-27 ℃, dropwise adding 1.3g of trimethylsilylacetylene into the reaction kettle, and preserving heat for 45min; monitoring the reaction end point by HPLC, and confirming that the central control is qualified;
30ml of water was added to a 100ml reaction flask, the temperature was lowered to 10-15℃and the reaction mixture was transferred. Dropwise adding 3.8g of 7M hydrochloric acid, stirring for 30min, detecting the pH value of the water phase to be 1.0, standing, separating liquid, retaining an organic phase, and concentrating and distilling the organic phase under reduced pressure to obtain a crude product; 30ml of acetone is added into the crude product of the distillation flask, and after stirring, the distillation under reduced pressure is continued to obtain the product. The yield is about 95.3 percent, and the purity of the product is 98.813 percent. The chromatogram is shown in FIG. 4.
(3) And filtering the water phase obtained by liquid separation to obtain the palladium-loaded titanium dioxide hollow nano microsphere catalyst, placing the catalyst in absolute ethyl alcohol, stirring and heating the catalyst at 60-70 ℃ by adopting a Soxhlet extractor, refluxing and washing the catalyst for 5 hours, activating the catalyst, and regenerating the catalyst.
(4) 0.048G of regenerated catalyst is taken and reacted according to the process of the step (2), and the purity of the obtained product is 97.74 percent, and the yield is 95.1 percent.
Example 2
(1) 30Ml of absolute ethanol was added to a 50ml three-necked round bottom flask, and 0.4ml of potassium nitrate solution (0.15 mol/L) was added dropwise thereto, followed by thoroughly stirring and mixing. 6ml of tetraisopropyl titanate was added and stirred vigorously until a white precipitate appeared. And (5) after sealing, standing and aging for 24 hours. And (3) after centrifugation and washing with purified water, drying at 60 ℃ to obtain the titanium dioxide precursor. Placing 0.2g of titanium dioxide precursor in a beaker, adding 40ml of 0.13wt.% H 2O2 solution, fully stirring, adding 0.45g of potassium hydroxide solid, placing the mixture in a hydrothermal kettle with a polytetrafluoroethylene lining, and carrying out hydrothermal reaction for 3.5 hours at 160 ℃; the resulting reaction was washed with centrifugation and absolute ethanol. The washed sample was added with 20ml of hydrochloric acid (0.1 mol/L) and immersed for 10 minutes. Obtaining a sample after centrifugation, absolute ethyl alcohol and deionized water washing; drying the sample at 60 ℃, grinding, and calcining at 650 ℃ for 3 hours to obtain the catalyst carrier titanium dioxide hollow nano-microsphere.
Adding 1g of titanium dioxide hollow nanospheres serving as a catalyst carrier into 30ml of deionized water, adding 0.1g of palladium dichloride, stirring for 3 hours at normal temperature, filtering, and drying the solid obtained by filtering at 60 ℃ to obtain the palladium-loaded titanium dioxide hollow nanospheres, wherein the load of palladium is 0.79% of the mass of the catalyst carrier. The transmission electron microscope of the catalyst is shown in figure 2.
(2) 36G of dichloromethane, 3g of 4-iodo-3-hydroxybenzoic acid methyl ester, 3.4g of triethylamine, 0.21g of cuprous iodide and 0.136g of triphenylphosphine are added into a 100ml reaction bottle, and after nitrogen replacement, 0.068g of palladium-loaded titanium dioxide hollow microsphere catalyst is added; controlling the temperature in the reaction kettle to be 20-27 ℃, dropwise adding 1.35g of trimethylsilylacetylene into the reaction kettle, and preserving heat for 50min; monitoring the reaction end point by HPLC, and confirming that the central control is qualified;
30ml of water was added to a 100ml reaction flask, the temperature was lowered to 10-15℃and the reaction mixture was transferred. 2.7g of 2M sulfuric acid is added dropwise, stirred for 30min, the pH value of the water phase is detected to be 1.6, the mixture is stood still, liquid separation is carried out, an organic phase is reserved, and the organic phase is concentrated and distilled under reduced pressure to obtain a crude product; 30ml of toluene is added into the crude product of the distillation flask, and after stirring, the distillation under reduced pressure is continued to obtain the product. The yield is about 95.8%, and the purity of the product is 98.727%. The chromatogram is shown in FIG. 5.
(3) And filtering the water phase obtained by liquid separation to obtain the palladium-loaded titanium dioxide hollow nano microsphere catalyst, placing the palladium-loaded titanium dioxide hollow nano microsphere catalyst in methyl tertiary butyl ether, stirring and heating the catalyst at 45-50 ℃ by adopting a Soxhlet extractor, refluxing and washing the catalyst for 6 hours, activating the catalyst, and regenerating the catalyst.
Example 3
(1) 30Ml of methanol was added to a 50ml three-necked round bottom flask, and 0.2ml of potassium nitrate solution (0.75 mol/L) was added dropwise thereto, followed by thoroughly stirring and mixing. 6ml of tetraisopropyl titanate was added and stirred vigorously until a white precipitate appeared. And (5) after sealing, standing and aging for 24 hours. And (3) after centrifugation and washing with purified water, drying at 60 ℃ to obtain the titanium dioxide precursor. Placing 0.2g of titanium dioxide precursor in a beaker, adding 40ml of 0.20wt.% H 2O2 solution, fully stirring, adding 0.45g of sodium hydroxide solid, placing the mixture in a hydrothermal kettle with a polytetrafluoroethylene lining, and carrying out hydrothermal reaction for 4.5 hours at 220 ℃; the resulting reaction was washed with centrifugation and absolute ethanol. The washed sample was added with 20ml of hydrochloric acid (0.1 mol/L) and immersed for 10 minutes. Obtaining a sample after centrifugation, absolute ethyl alcohol and deionized water washing; drying the sample at 60 ℃, grinding, and calcining at 500 ℃ for 8 hours to obtain the catalyst carrier titanium dioxide hollow nano-microsphere.
Adding 1g of titanium dioxide hollow nanospheres serving as a catalyst carrier into 30ml of deionized water, adding 0.1g of palladium dichloride, stirring for 3 hours at normal temperature, filtering, and drying the solid obtained by filtering at 60 ℃ to obtain the palladium-loaded titanium dioxide hollow nanospheres, wherein the load of palladium is 0.81% of the mass of the catalyst carrier. The transmission electron microscope of the catalyst is shown in figure 3.
(2) 36G of dichloromethane, 3g of 4-iodo-3-hydroxybenzoic acid methyl ester, 3.5g of triethylamine, 0.20g of cuprous iodide and 0.130g of triphenylphosphine are added into a 100ml reaction bottle, and after nitrogen replacement, 0.10g of palladium-loaded titanium dioxide hollow microsphere catalyst is added; controlling the temperature in the reaction kettle to be 20-27 ℃, dropwise adding 1.33g of trimethylsilylacetylene into the reaction kettle, and preserving the heat for 48min; monitoring the reaction end point by HPLC, and confirming that the central control is qualified;
30ml of water was added to a 100ml reaction flask, the temperature was lowered to 10-15℃and the reaction mixture was transferred. Dropwise adding 6.6g of 5M nitric acid, stirring for 30min, detecting the pH value of the water phase to be 2.69, standing, separating liquid, retaining an organic phase, and concentrating and distilling the organic phase under reduced pressure to obtain a crude product; 30ml of methanol is added into the crude product of the distillation flask, and after stirring, the distillation under reduced pressure is continued to obtain the product. The yield is about 96.2%, and the purity of the product is 98.874%. The chromatogram is shown in FIG. 6.
(3) And filtering the water phase obtained by liquid separation to obtain the palladium-loaded titanium dioxide hollow nano microsphere catalyst, placing the palladium-loaded titanium dioxide hollow nano microsphere catalyst in methanol, stirring and heating the catalyst at 55-60 ℃ by adopting a Soxhlet extractor, refluxing and washing the catalyst for 5 hours, activating the catalyst, and regenerating the catalyst.
The stability acceleration test was performed on the methyl 3-hydroxy-4- ((trimethylsilyl) ethynyl) benzoate product of examples 1-3 as follows:
Taking 8g of each product of examples 1-3, respectively, dividing the average into 4 parts, putting 2g of each part into 7 x 10cm plastic package bags, vacuum packaging by using a tin foil bag, and putting into a stability acceleration test box; the mixture was left for 15 days at a temperature of 40.+ -. 2 ℃ and a relative humidity of 75%.+ -. 5%. The test was performed at the end of the test period, at the end of day 2, at the end of day 5, at the end of day 10, and at the end of day 15 by sampling once. The stability of the samples was examined and the data is recorded in table 1.
TABLE 1 results of stability test on the products of examples 1-3
Claims (9)
1. A method for catalytic synthesis of methyl 3-hydroxy-4- ((trimethylsilyl) ethynyl) benzoate, which is characterized by comprising the following steps: under the action of a palladium-loaded titanium dioxide hollow nano microsphere catalyst, 4-iodo-3-hydroxy methyl benzoate reacts with trimethylsilylacetylene to generate 3-hydroxy-4- ((trimethylsilyl) ethynyl) methyl benzoate; the preparation method of the palladium-loaded titanium dioxide hollow nanoparticle catalyst comprises the steps of firstly taking tetraisopropyl titanate as a raw material, synthesizing a titanium dioxide precursor by an aging method, preparing the titanium dioxide hollow nanoparticle by a hydrothermal method, and finally loading palladium on the titanium dioxide hollow nanoparticle;
the preparation method of the palladium-loaded titanium dioxide hollow nanoparticle catalyst comprises the following steps:
(1) Transferring the potassium nitrate solution into an organic solvent, mixing, adding tetraisopropyl titanate, stirring, ageing and centrifuging to obtain a titanium dioxide precursor;
(2) Adding titanium dioxide precursor into hydrogen peroxide, adding alkali, mixing, performing hydrothermal reaction, centrifuging after the reaction is finished to obtain precipitate, washing, transferring into acid liquor, centrifuging, washing, and calcining to obtain titanium dioxide hollow nano microspheres;
(3) The hollow titanium dioxide microsphere reacts with palladium dichloride to obtain the palladium-loaded hollow titanium dioxide microsphere catalyst.
2. The method for catalytic synthesis of methyl 3-hydroxy-4- ((trimethylsilyl) ethynyl) benzoate according to claim 1, wherein: the palladium loading amount in the palladium loaded titanium dioxide hollow nano microsphere catalyst is 0.05-1.5% of the mass of the catalyst carrier; the mass of the palladium-loaded titanium dioxide hollow nano microsphere catalyst is 1.5-3.5% of the mass of the 4-iodine-3-hydroxybenzoic acid methyl ester.
3. The method for catalytic synthesis of methyl 3-hydroxy-4- ((trimethylsilyl) ethynyl) benzoate according to claim 1, wherein: in the step (1), the concentration of the potassium nitrate solution is 0.05-1.15mol/L, the organic solvent is one or more of absolute ethyl alcohol, methanol, isopropanol or toluene, the aging time is 12-48 hours, and the volume and use ratio of the potassium nitrate solution to the tetraisopropyl titanate is 0.15-0.75:6.
4. The method for catalytic synthesis of methyl 3-hydroxy-4- ((trimethylsilyl) ethynyl) benzoate according to claim 1, wherein: in the step (2), the concentration of the hydrogen peroxide is 0.01-0.35wt.%; the alkali is one or more of sodium hydroxide, potassium hydroxide or aluminum hydroxide; the hydrothermal reaction temperature is 120-300 ℃, and the hydrothermal reaction time is 1-6 hours; the calcination temperature is 250-800 ℃; the washing solvent is one or more of absolute ethyl alcohol, methanol, toluene, acetone or methyl tertiary butyl ether; the dosage ratio of the hydrogen peroxide to the titanium dioxide precursor to the alkali is 40-45:0.2:0.35-0.55, wherein the hydrogen peroxide is calculated by ml, and the titanium dioxide precursor and the alkali are calculated by g.
5. The method for catalytic synthesis of methyl 3-hydroxy-4- ((trimethylsilyl) ethynyl) benzoate according to claim 1, wherein: in the step (3), the reaction system of the titanium dioxide hollow nano-microspheres and palladium dichloride is one or more of deionized water, methanol, ethanol or ethyl acetate.
6. A method for the catalytic synthesis of methyl 3-hydroxy-4- ((trimethylsilyl) ethynyl) benzoate according to claim 1, characterised in that it comprises the steps of:
(1) Mixing an organic solvent, 4-iodine-3-hydroxybenzoic acid methyl ester, an alkaline solvent, cuprous iodide and triphenylphosphine, performing nitrogen substitution, adding a palladium-loaded titanium dioxide hollow nanoparticle catalyst, controlling the temperature of a reaction system, dropwise adding trimethylsilylacetylene, keeping the temperature for reaction after the dropwise addition is finished, and monitoring the end point of the reaction by HPLC;
(2) Adding the reaction solution after the reaction into water, dropwise adding acid liquor, adjusting the pH value of the system to be strong acid, standing, separating the solution, and distilling the organic phase to obtain a crude product; adding an organic solvent into the crude product, and distilling to obtain 3-hydroxy-4- ((trimethylsilyl) ethynyl) methyl benzoate;
(3) And filtering the water phase obtained by liquid separation to obtain the palladium-loaded titanium dioxide hollow nano microsphere catalyst, washing by an organic solvent, activating and recycling.
7. The method for catalytic synthesis of methyl 3-hydroxy-4- ((trimethylsilyl) ethynyl) benzoate according to claim 6, wherein: in the step (1), the organic solvent is one or more of toluene, dichloromethane or chloroform; the alkaline solvent is one or more of triethylamine, diethylamine, tetramethyl ethylenediamine and 1, 8-diazabicyclo undec-7-ene; the mass of the cuprous iodide is 4-9% of the mass of the 4-iodo-3-hydroxybenzoic acid methyl ester, the mass of the triphenylphosphine is 45-75% of the mass of the cuprous iodide, and the mass ratio of the trimethylsilylacetylene to the 4-iodo-3-hydroxybenzoic acid methyl ester is 1.20-1.40:3.
8. The method for catalytic synthesis of methyl 3-hydroxy-4- ((trimethylsilyl) ethynyl) benzoate according to claim 6, wherein: in the step (2), the acid liquor is one or more of 6-8M hydrochloric acid, 2-3M sulfuric acid or 4-6M nitric acid, the strong acid pH value range is 0.5-3.3, and the organic solvent is one or more of methanol, ethanol, isopropanol, acetone, butanone or toluene.
9. The method for catalytic synthesis of methyl 3-hydroxy-4- ((trimethylsilyl) ethynyl) benzoate according to claim 6, wherein: in the step (3), the organic solvent is one or more of methanol, absolute ethyl alcohol, isopropanol, acetone, methyl tertiary butyl ether, diethyl ether, n-heptane or n-hexane; the washing adopts reflux washing, and the reflux washing time is 4-9 hours.
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| CN105523583A (en) * | 2014-10-22 | 2016-04-27 | 中国石油化工股份有限公司 | Synthetic method of nano titanium dioxide powder |
| CN108906134A (en) * | 2018-07-06 | 2018-11-30 | 河北大学 | A kind of titanic oxide material, preparation method and load type palladium catalyst |
| CN108940271A (en) * | 2018-07-04 | 2018-12-07 | 肇庆市创业帮信息技术有限公司 | A kind of titania-silica compound loaded palladium catalyst and the preparation method and application thereof |
| CN112625057A (en) * | 2020-12-25 | 2021-04-09 | 山东金城柯瑞化学有限公司 | Synthetic method of methyl 3-hydroxy-4- ((trimethylsilyl) ethynyl) benzoate |
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| CN108940271A (en) * | 2018-07-04 | 2018-12-07 | 肇庆市创业帮信息技术有限公司 | A kind of titania-silica compound loaded palladium catalyst and the preparation method and application thereof |
| CN108906134A (en) * | 2018-07-06 | 2018-11-30 | 河北大学 | A kind of titanic oxide material, preparation method and load type palladium catalyst |
| CN112625057A (en) * | 2020-12-25 | 2021-04-09 | 山东金城柯瑞化学有限公司 | Synthetic method of methyl 3-hydroxy-4- ((trimethylsilyl) ethynyl) benzoate |
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