CN114315577A - Synthesis method of 2-ethoxymethylene-4, 4-difluoroacetoacetic acid ethyl ester - Google Patents
Synthesis method of 2-ethoxymethylene-4, 4-difluoroacetoacetic acid ethyl ester Download PDFInfo
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- KDVPGBVZKTVEIS-UHFFFAOYSA-N ethyl 2-(ethoxymethylidene)-4,4-difluoro-3-oxobutanoate Chemical compound CCOC=C(C(=O)C(F)F)C(=O)OCC KDVPGBVZKTVEIS-UHFFFAOYSA-N 0.000 title claims abstract description 26
- 238000001308 synthesis method Methods 0.000 title claims abstract description 22
- 229920000515 polycarbonate Polymers 0.000 claims abstract description 96
- 239000004417 polycarbonate Substances 0.000 claims abstract description 96
- 150000002736 metal compounds Chemical class 0.000 claims abstract description 73
- 239000002131 composite material Substances 0.000 claims abstract description 72
- 239000003054 catalyst Substances 0.000 claims abstract description 64
- 238000006243 chemical reaction Methods 0.000 claims abstract description 28
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 claims abstract description 25
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims abstract description 21
- 238000000034 method Methods 0.000 claims abstract description 19
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 claims abstract description 19
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 claims abstract description 16
- 238000010189 synthetic method Methods 0.000 claims abstract description 15
- 239000002994 raw material Substances 0.000 claims abstract description 14
- 229910021627 Tin(IV) chloride Inorganic materials 0.000 claims abstract description 13
- 230000009471 action Effects 0.000 claims abstract description 11
- 230000008569 process Effects 0.000 claims abstract description 8
- -1 2-ethoxy Chemical group 0.000 claims abstract description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 24
- CBDPWKVOPADMJC-UHFFFAOYSA-N ethyl 4,4-difluoro-3-oxobutanoate Chemical compound CCOC(=O)CC(=O)C(F)F CBDPWKVOPADMJC-UHFFFAOYSA-N 0.000 claims description 22
- 238000001914 filtration Methods 0.000 claims description 15
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 claims description 12
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 12
- 239000003960 organic solvent Substances 0.000 claims description 11
- 239000011259 mixed solution Substances 0.000 claims description 10
- 125000003118 aryl group Chemical group 0.000 claims description 8
- 230000003100 immobilizing effect Effects 0.000 claims description 8
- 229920005668 polycarbonate resin Polymers 0.000 claims description 8
- 239000004431 polycarbonate resin Substances 0.000 claims description 8
- 238000010992 reflux Methods 0.000 claims description 8
- 238000003756 stirring Methods 0.000 claims description 8
- 238000001035 drying Methods 0.000 claims description 7
- 238000003786 synthesis reaction Methods 0.000 claims description 7
- XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical group ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 claims description 6
- 238000004321 preservation Methods 0.000 claims description 6
- 230000002194 synthesizing effect Effects 0.000 claims description 6
- UBOXGVDOUJQMTN-UHFFFAOYSA-N trichloroethylene Natural products ClCC(Cl)Cl UBOXGVDOUJQMTN-UHFFFAOYSA-N 0.000 claims description 6
- 230000015572 biosynthetic process Effects 0.000 claims description 3
- 238000001816 cooling Methods 0.000 claims description 3
- 238000010438 heat treatment Methods 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 3
- 238000005406 washing Methods 0.000 claims description 3
- 239000002904 solvent Substances 0.000 abstract description 6
- 238000002360 preparation method Methods 0.000 abstract description 4
- 230000009286 beneficial effect Effects 0.000 abstract description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 21
- 150000002148 esters Chemical class 0.000 description 18
- 239000000203 mixture Substances 0.000 description 12
- 239000002244 precipitate Substances 0.000 description 8
- 239000007788 liquid Substances 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 230000000052 comparative effect Effects 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 238000010907 mechanical stirring Methods 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- RLOHOBNEYHBZID-UHFFFAOYSA-N 3-(difluoromethyl)-1-methylpyrazole-4-carboxylic acid Chemical compound CN1C=C(C(O)=O)C(C(F)F)=N1 RLOHOBNEYHBZID-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 239000003899 bactericide agent Substances 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 230000007797 corrosion Effects 0.000 description 2
- 238000005260 corrosion Methods 0.000 description 2
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- 238000011084 recovery Methods 0.000 description 2
- 238000007086 side reaction Methods 0.000 description 2
- ZMYFCFLJBGAQRS-IRXDYDNUSA-N (2R,3S)-epoxiconazole Chemical compound C1=CC(F)=CC=C1[C@@]1(CN2N=CN=C2)[C@H](C=2C(=CC=CC=2)Cl)O1 ZMYFCFLJBGAQRS-IRXDYDNUSA-N 0.000 description 1
- XTDZGXBTXBEZDN-UHFFFAOYSA-N 3-(difluoromethyl)-N-(9-isopropyl-1,2,3,4-tetrahydro-1,4-methanonaphthalen-5-yl)-1-methylpyrazole-4-carboxamide Chemical compound CC(C)C1C2CCC1C1=C2C=CC=C1NC(=O)C1=CN(C)N=C1C(F)F XTDZGXBTXBEZDN-UHFFFAOYSA-N 0.000 description 1
- 239000005737 Benzovindiflupyr Substances 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
- 229940124186 Dehydrogenase inhibitor Drugs 0.000 description 1
- 239000005767 Epoxiconazole Substances 0.000 description 1
- 239000005788 Fluxapyroxad Substances 0.000 description 1
- 239000005799 Isopyrazam Substances 0.000 description 1
- CCCGEKHKTPTUHJ-UHFFFAOYSA-N N-[9-(dichloromethylene)-1,2,3,4-tetrahydro-1,4-methanonaphthalen-5-yl]-3-(difluoromethyl)-1-methylpyrazole-4-carboxamide Chemical compound FC(F)C1=NN(C)C=C1C(=O)NC1=CC=CC2=C1C1CCC2C1=C(Cl)Cl CCCGEKHKTPTUHJ-UHFFFAOYSA-N 0.000 description 1
- 239000005869 Pyraclostrobin Substances 0.000 description 1
- 102000019259 Succinate Dehydrogenase Human genes 0.000 description 1
- 108010012901 Succinate Dehydrogenase Proteins 0.000 description 1
- 238000007036 catalytic synthesis reaction Methods 0.000 description 1
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- 150000001875 compounds Chemical class 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- SXSGXWCSHSVPGB-UHFFFAOYSA-N fluxapyroxad Chemical compound FC(F)C1=NN(C)C=C1C(=O)NC1=CC=CC=C1C1=CC(F)=C(F)C(F)=C1 SXSGXWCSHSVPGB-UHFFFAOYSA-N 0.000 description 1
- VUZPPFZMUPKLLV-UHFFFAOYSA-N methane;hydrate Chemical compound C.O VUZPPFZMUPKLLV-UHFFFAOYSA-N 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- HZRSNVGNWUDEFX-UHFFFAOYSA-N pyraclostrobin Chemical compound COC(=O)N(OC)C1=CC=CC=C1COC1=NN(C=2C=CC(Cl)=CC=2)C=C1 HZRSNVGNWUDEFX-UHFFFAOYSA-N 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
Abstract
The invention discloses a synthesis method of 2-ethoxy methylene-4, 4-difluoro ethyl acetoacetate, which takes 4, 4-difluoro ethyl acetoacetate and triethyl orthoformate as raw materials to synthesize 2-ethoxy methylene-4, 4-difluoro ethyl acetoacetate under the action of a polycarbonate catalyst immobilized with a composite metal compound, wherein the polycarbonate catalyst immobilized with the composite metal compound comprises polycarbonate and the composite metal compound immobilized on the polycarbonate, and the composite metal compound comprises two or three of aluminum trichloride, titanium tetrachloride and tin tetrachloride. The synthetic method of the 2-ethoxymethylene-4, 4-difluoroacetoacetic acid ethyl ester has the advantages of simple process, convenient operation, lower cost, no solvent, high reaction rate, high yield and the like, is suitable for large-scale preparation, is beneficial to industrial application, and has high use value and good application prospect.
Description
Technical Field
The invention belongs to the technical field of compound intermediate synthesis, and relates to a synthetic method of 2-ethoxymethylene-4, 4-difluoroacetoacetic acid ethyl ester.
Background
Ethyl 2-ethoxymethylene-4, 4-difluoroacetoacetate is an important pesticide intermediate, and is mainly used for preparing an intermediate 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid. The 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid is an important intermediate for synthesizing succinate dehydrogenase inhibitor (SDHI) bactericides, and the main varieties of the SDHI bactericides synthesized by using the intermediate are fluxapyroxad, benzovindiflupyr, pyraclostrobin, epoxiconazole, isopyrazam and the like.
At present, the commonly adopted synthesis process is to synthesize 2-ethoxymethylene-4, 4-difluoroacetoacetic acid ethyl ester by using 4, 4-difluoroacetoacetic acid ethyl ester and triethyl orthoformate as starting raw materials under the action of acetic anhydride. For example, patent documents such as CN104379551A, CN101959840A, WO/2013/118071A1 and WO/2009/012482A2 are reported. However, in the above synthesis method, the reaction is carried out at 90-120 ℃ in an acetic anhydride system, and after the reaction is finished, excessive acetic anhydride and byproducts such as ethyl acetate and acetic acid must be removed by concentration, so that the problems of complicated operation, more byproducts, low yield and the like exist.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provide a synthetic method of 2-ethoxymethylene-4, 4-difluoroacetoacetic acid ethyl ester, which has the advantages of simple process, convenient operation, lower cost, no solvent, high reaction rate and high yield.
In order to solve the technical problems, the invention adopts the technical scheme that:
a synthetic method of 2-ethoxymethylene-4, 4-difluoro ethyl acetoacetate is characterized in that 4, 4-difluoro ethyl acetoacetate and triethyl orthoformate are used as raw materials, and the 2-ethoxymethylene-4, 4-difluoro ethyl acetoacetate is synthesized under the action of a polycarbonate catalyst of an immobilized composite metal compound; the polycarbonate catalyst for immobilizing the composite metal compound comprises polycarbonate and the composite metal compound immobilized on the polycarbonate, wherein the composite metal compound comprises two or three of aluminum trichloride, titanium tetrachloride and tin tetrachloride.
In the synthesis method, the polycarbonate catalyst for immobilizing the composite metal compound is further improved by the following method: adding the composite metal compound into an organic solvent, stirring, heating to reflux, dropwise adding a mixed solution of polycarbonate and the organic solvent, carrying out heat preservation reaction after dropwise adding is finished, and obtaining the polycarbonate catalyst for immobilized composite metal compound after cooling, filtering, washing and drying.
The synthesis method is further improved, wherein the mass ratio of the composite metal compound to the polycarbonate is 2-3: 1.0; the molar ratio of each component in the composite metal compound is 1:1 or 1:1: 1; the organic solvent is any one of tetrahydrofuran, carbon tetrachloride and trichloroethylene; the polycarbonate is an aromatic polycarbonate resin.
In the synthesis method, the mixed solution of the polycarbonate and the organic solvent is dropwise added within 1-3 h.
The synthesis method is further improved, and the time of the heat preservation reaction is 2-5 h; the drying is carried out under vacuum conditions; the drying time is 5-10 h.
The synthesis method is further improved and comprises the following steps: mixing 4, 4-difluoro ethyl acetoacetate and triethyl orthoformate with a polycarbonate catalyst of an immobilized composite metal compound for synthetic reaction, and filtering to obtain 2-ethoxy methylene-4, 4-difluoro ethyl acetoacetate.
In the synthesis method, the mass ratio of the 4, 4-difluoroacetoacetic acid ethyl ester to the polycarbonate catalyst of the immobilized composite metal compound is further improved to be 1.0: 0.05-0.2.
In the synthesis method, the molar ratio of the ethyl 4, 4-difluoroacetoacetate to the triethyl orthoformate is further improved to be 1.0: 1.05-1.5.
The synthesis method is further improved, and the synthesis reaction is carried out at the temperature of 80-110 ℃; the time of the synthesis reaction is 1-5 h.
In a further improvement of the above synthesis method, the filtration step further comprises: and continuously using the polycarbonate catalyst of the solid-supported composite metal compound obtained after filtration for synthesizing 2-ethoxymethylene-4, 4-difluoroacetoacetic acid ethyl ester.
Compared with the prior art, the invention has the advantages that:
(1) the invention provides a synthesis method of 2-ethoxymethylene-4, 4-difluoroethyl acetoacetate, which is characterized in that 4, 4-difluoroethyl acetoacetate and triethyl orthoformate are used as raw materials, and the 2-ethoxymethylene-4, 4-difluoroethyl acetoacetate is synthesized under the action of a polycarbonate catalyst for immobilizing a composite metal compound, wherein the polycarbonate catalyst for immobilizing the composite metal compound comprises polycarbonate and the composite metal compound immobilized on the polycarbonate, and the composite metal compound comprises two or three of aluminum trichloride, titanium tetrachloride and tin tetrachloride. Compared with the polycarbonate catalyst immobilized with a single metal compound, in the polycarbonate catalyst immobilized with the composite metal compound, unsaturated pi bonds in a polycarbonate skeleton can form a stable coordination structure with the composite metal compound, and the polycarbonate catalyst immobilized with the composite metal compound has higher catalytic activity and use stability, so when the polycarbonate catalyst immobilized with the composite metal compound is used for catalytically synthesizing 2-ethoxymethylene-4, 4-difluoroacetoacetic acid ethyl ester, the reaction yield and the reaction rate are improved, the polycarbonate catalyst is easy to separate from reaction liquid after the reaction is finished, the operation flow is simplified, meanwhile, acetic anhydride is not needed to be used as a solvent, the consumption of raw material triethyl orthoformate can be reduced, the side reactions are less, the production cost is greatly reduced, the content of impurities is reduced, desolventizing treatment is not needed after the reaction is finished, and the target product can be obtained after the catalyst is removed by filtering, the production efficiency is improved, the recovery and the reutilization of the catalyst are realized, and meanwhile, the influence of corrosion on equipment caused by the use of acetic anhydride can be avoided. The synthetic method of the 2-ethoxymethylene-4, 4-difluoroacetoacetic acid ethyl ester has the advantages of simple process, convenient operation, lower cost, no solvent, high reaction rate, high yield and the like, is suitable for large-scale preparation, is beneficial to industrial application, and has high use value and good application prospect.
(2) In the invention, the polycarbonate catalyst of the immobilized composite metal compound has good stability of the effective components, and the filtered catalyst can be recycled for multiple times, thereby improving the utilization efficiency of the catalyst, saving the cost and having high industrial application value.
Detailed Description
The invention is further described below with reference to specific preferred embodiments, without thereby limiting the scope of protection of the invention.
The raw materials and instruments used in the following examples are all commercially available; the equipment and the preparation process are conventional equipment and conventional process unless otherwise specified.
Examples
A synthetic method of 2-ethoxymethylene-4, 4-difluoroacetoacetic ester takes 4, 4-difluoroacetoacetic ester and triethyl orthoformate as raw materials, and synthesizes the 2-ethoxymethylene-4, 4-difluoroacetoacetic ester under the action of a polycarbonate catalyst of an immobilized composite metal compound, which comprises the following steps: mixing 4, 4-difluoroacetoacetic acid ethyl ester, triethyl orthoformate and the polycarbonate catalyst of the immobilized composite metal compound according to the mass ratio of 1.0: 0.05-0.2 and the molar ratio of 1.0: 1.05-1.5 of the 4, 4-difluoroacetoacetic acid ethyl ester to the polycarbonate catalyst of the immobilized composite metal compound, carrying out synthetic reaction for 1-5 h at the temperature of 80-110 ℃, and filtering to obtain the 2-ethoxymethylene-4, 4-difluoroacetoacetic acid ethyl ester. In the synthesis method of the invention, after the filtration is finished, the method further comprises the following steps: and continuously using the polycarbonate catalyst of the solid-supported composite metal compound obtained after filtration for synthesizing 2-ethoxymethylene-4, 4-difluoroacetoacetic acid ethyl ester.
In the invention, the polycarbonate catalyst used for immobilizing the composite metal compound comprises polycarbonate and the composite metal compound immobilized on the polycarbonate, wherein the composite metal compound comprises two or three of aluminum trichloride, titanium tetrachloride and tin tetrachloride.
In the invention, the polycarbonate catalyst for immobilizing the composite metal compound is prepared by the following method: adding the composite metal compound into an organic solvent according to the mass ratio of the composite metal compound to the polycarbonate of 2-3: 1.0, stirring, heating to reflux, dropwise adding a mixed solution of the polycarbonate and the organic solvent, after dropwise adding within 1-3 h, carrying out heat preservation reaction for 2-5 h after dropwise adding is finished, cooling, filtering, washing, and drying for 5-10 h under a vacuum condition to obtain the polycarbonate catalyst for immobilized composite metal compound. In the invention, the molar ratio of each component in the composite metal compound is 1:1 or 1:1:1, the organic solvent is any one of tetrahydrofuran, carbon tetrachloride and trichloroethylene, and the polycarbonate is aromatic polycarbonate resin.
Example 1:
a synthetic method of 2-ethoxymethylene-4, 4-difluoroacetoacetic ester takes 4, 4-difluoroacetoacetic ester and triethyl orthoformate as raw materials, and synthesizes the 2-ethoxymethylene-4, 4-difluoroacetoacetic ester under the action of a polycarbonate catalyst of an immobilized composite metal compound, which comprises the following steps:
169.5g of 4, 4-difluoroacetoacetic acid ethyl ester (98%, 1.0mol), 157.2g of triethyl orthoformate (99%, 1.05mol) and 17.0g of a polycarbonate catalyst (polycarbonate with aluminum trichloride/titanium tetrachloride) which supports a composite metal compound were put into a four-necked flask (1000mL) equipped with a mechanical stirrer, a condenser tube, a constant pressure dropping funnel and a thermometer, and stirred to react at 80 ℃ for 5 hours, cooled to 15 ℃ and filtered to obtain 323.8g of pale yellow liquid ethyl 2-ethoxymethylene-4, 4-difluoroacetoacetate with a content of 66.5% and a yield of 96.9% (based on 4, 4-difluoroacetoacetic acid ethyl ester).
In this example, the polycarbonate catalyst (polycarbonate with aluminum trichloride/titanium tetrachloride supported thereon) supporting the composite metal compound used was prepared by the following method:
36.2g of tetrahydrofuran (99.5 percent, 0.5mol) is added into a four-mouth bottle (250mL) provided with a mechanical stirring device, a condenser tube, a constant pressure dropping funnel and a thermometer, 13.5g of anhydrous aluminum trichloride (99 percent, 0.1mol) and 19.1 g of titanium tetrachloride (99 percent, 0.1mol) are added under the stirring condition, the mixture is uniformly mixed and heated to reflux, a mixed solution containing 16.3g of aromatic polycarbonate resin and 36.2g of tetrahydrofuran (99.5 percent, 0.5mol) is slowly dripped, the 1h dripping is controlled to be finished, the temperature is kept for 5h, the reaction is reduced to low temperature, the mixture is filtered, precipitates are respectively washed by tetrahydrofuran and water, and then the precipitates are dried for 5h under the vacuum condition, and 35.2g of polycarbonate catalyst (polycarbonate of immobilized composite metal compounds) is obtained.
Example 2:
a synthetic method of 2-ethoxymethylene-4, 4-difluoroacetoacetic ester takes 4, 4-difluoroacetoacetic ester and triethyl orthoformate as raw materials, and synthesizes the 2-ethoxymethylene-4, 4-difluoroacetoacetic ester under the action of a polycarbonate catalyst of an immobilized composite metal compound, which comprises the following steps:
169.5g of 4, 4-difluoroacetoacetic acid ethyl ester (98%, 1.0mol), 164.7g of triethyl orthoformate (99%, 1.1mol) and 33.9g of a polycarbonate catalyst (polycarbonate with aluminum trichloride/tin tetrachloride) immobilized thereon for supporting a complex metal compound were put into a four-necked flask (1000mL) equipped with a mechanical stirrer, a condenser tube, a constant pressure dropping funnel and a thermometer, and stirred at 110 ℃ for 1 hour, cooled to 15 ℃ and filtered to obtain 330.2g of pale yellow liquid ethyl 2-ethoxymethylene-4, 4-difluoroacetoacetate with a content of 65.3% and a yield of 97.1% (based on the 4, 4-difluoroacetoacetic acid ethyl ester).
In this example, the polycarbonate catalyst (polycarbonate with aluminum trichloride/tin tetrachloride immobilized thereon) used for supporting the composite metal compound was prepared by the following method:
77.7g of carbon tetrachloride (99 percent, 0.5mol) is added into a four-mouth bottle (250mL) provided with a mechanical stirring device, a condenser tube, a constant-pressure dropping funnel and a thermometer, 13.5g of anhydrous aluminum trichloride (99 percent, 0.1mol) and 26.3g of anhydrous tin tetrachloride (99 percent, 0.1mol) are added under the stirring condition, the mixture is uniformly mixed and heated to reflux, a mixed solution containing 13.3g of aromatic polycarbonate resin and 77.7g of carbon tetrachloride (99 percent, 0.5mol) is slowly dripped, the dripping is controlled to be finished for 2h, the heat preservation reaction is carried out for 2h, the temperature is reduced to low temperature, the precipitate is filtered, washed by carbon tetrachloride and water respectively, and dried for 10h under the vacuum condition, and 40.5g of polycarbonate catalyst (aluminum trichloride/tin tetrachloride) with immobilized composite metal compounds is obtained.
Example 3:
a synthetic method of 2-ethoxymethylene-4, 4-difluoroacetoacetic ester takes 4, 4-difluoroacetoacetic ester and triethyl orthoformate as raw materials, and synthesizes the 2-ethoxymethylene-4, 4-difluoroacetoacetic ester under the action of a polycarbonate catalyst of an immobilized composite metal compound, which comprises the following steps:
169.5g of 4, 4-difluoroacetoacetic acid ethyl ester (98%, 1.0mol), 224.5g of triethyl orthoformate (99%, 1.5mol) and 8.5g of a polycarbonate catalyst (polycarbonate with immobilized aluminum trichloride/titanium tetrachloride/tin tetrachloride) for immobilizing a composite metal compound were put into a four-necked flask (1000mL) equipped with a mechanical stirrer, a condenser tube, a constant pressure dropping funnel and a thermometer, and stirred at 90 ℃ for 4 hours, cooled to 15 ℃ and filtered to obtain 391.5g of pale yellow liquid ethyl 2-ethoxymethylene-4, 4-difluoroacetoacetate with a content of 55.3% and a yield of 97.5% (based on the 4, 4-difluoroacetoacetic acid ethyl ester).
In this example, the polycarbonate catalyst (polycarbonate having aluminum trichloride/titanium tetrachloride/tin tetrachloride immobilized thereon) supporting the composite metal compound used was prepared by the following method:
66.4g of trichloroethylene (99 percent, 0.5mol) is added into a four-mouth bottle (250mL) provided with a mechanical stirring device, a condenser tube, a constant pressure dropping funnel and a thermometer, 13.5g of anhydrous aluminum trichloride (99 percent, 0.1mol), 19.1 g of titanium tetrachloride (99 percent, 0.1mol) and 26.3g of anhydrous tin tetrachloride (99 percent, 0.1mol) are added under the stirring condition, the mixture is uniformly mixed and heated to reflux, a mixed solution containing 19.6g of aromatic polycarbonate resin and 66.4g of trichloroethylene (99 percent, 0.5mol) is slowly dripped at the beginning, after 3h dripping is controlled, the temperature is kept for reaction for 3h, the temperature is reduced to low temperature, the mixture is filtered, precipitates are respectively washed by trichloroethylene and water, and then the precipitates are dried for 6h under the vacuum condition, and 61.3g of polycarbonate catalyst (polycarbonate of immobilized aluminum trichloride/titanium tetrachloride/tin tetrachloride) of immobilized composite metal compounds is obtained.
Example 4:
a synthetic method of 2-ethoxymethylene-4, 4-difluoroacetoacetic ester takes 4, 4-difluoroacetoacetic ester and triethyl orthoformate as raw materials, and synthesizes the 2-ethoxymethylene-4, 4-difluoroacetoacetic ester under the action of a polycarbonate catalyst of an immobilized composite metal compound, which comprises the following steps:
169.5g of 4, 4-difluoroacetoacetic acid ethyl ester (98%, 1.0mol), 157.2g of triethyl orthoformate (99%, 1.05mol) and 17.0g of a polycarbonate catalyst (polycarbonate with titanium tetrachloride/tin tetrachloride) which supports a composite metal compound were charged into a four-necked flask (1000mL) equipped with a mechanical stirrer, a condenser, a constant pressure dropping funnel and a thermometer, and the mixture was stirred at 80 ℃ for 1 hour, cooled to 15 ℃ and filtered to obtain 324.1g of pale yellow liquid ethyl 2-ethoxymethylene-4, 4-difluoroacetoacetate with a content of 65.9% and a yield of 96.2% (based on the 4, 4-difluoroacetoacetic acid ethyl ester).
In this example, the polycarbonate catalyst supporting the composite metal compound (titanium tetrachloride/tin tetrachloride-supported polycarbonate) used was prepared by the following method:
36.2g of tetrahydrofuran (99.5%, 0.5mol) was charged into a four-necked flask (250mL) equipped with a mechanical stirrer, a condenser tube, a constant pressure dropping funnel and a thermometer, 19.1 g of titanium tetrachloride (99%, 0.1mol) and 26.3g of anhydrous tin tetrachloride (99%, 0.1mol) were added under stirring, the mixture was uniformly mixed, heated to reflux, a mixed solution containing 22.7g of an aromatic polycarbonate resin and 36.2g of tetrahydrofuran (99.5%, 0.5mol) was slowly dropped into the flask, after controlling the dropping for 2 hours, the reaction was carried out for 5 hours while maintaining the temperature, cooled to a low temperature, filtered, and the precipitate was washed with tetrahydrofuran and water, and dried under vacuum for 5 hours to obtain 46.7g of a composite metal compound-supported polycarbonate catalyst (titanium tetrachloride/tin tetrachloride-supported polycarbonate).
Example 5:
a synthetic method of 2-ethoxymethylene-4, 4-difluoroacetoacetic ester takes 4, 4-difluoroacetoacetic ester and triethyl orthoformate as raw materials, and synthesizes the 2-ethoxymethylene-4, 4-difluoroacetoacetic ester under the action of a polycarbonate catalyst of an immobilized composite metal compound, which comprises the following steps:
169.5g of 4, 4-difluoroacetoacetic acid ethyl ester (98%, 1.0mol), 157.2g of triethyl orthoformate (99%, 1.05mol) and 17.0g of a polycarbonate catalyst (polycarbonate with titanium tetrachloride/tin tetrachloride) which supports a composite metal compound were charged into a four-necked flask (1000mL) equipped with a mechanical stirrer, a condenser tube, a constant pressure dropping funnel and a thermometer, and the mixture was stirred at 100 ℃ for 2 hours, cooled to 15 ℃ and filtered to obtain 321.6g of pale yellow liquid ethyl 2-ethoxymethylene-4, 4-difluoroacetoacetate with a content of 66.7% and a yield of 96.6% (based on the 4, 4-difluoroacetoacetic acid ethyl ester).
In this example, the composite metal compound-immobilized polycarbonate catalyst (titanium tetrachloride/tin tetrachloride-immobilized polycarbonate) used was the composite metal compound-immobilized polycarbonate catalyst (titanium tetrachloride/tin tetrachloride-immobilized polycarbonate) obtained by filtration in example 4.
Comparative example 1:
a synthetic method of 2-ethoxymethylene-4, 4-difluoroacetoacetic acid ethyl ester comprises the following steps:
169.5g of 4, 4-difluoroacetoacetic acid ethyl ester (98%, 1.0mol), 157.2g of triethyl orthoformate (99%, 1.05mol) and 13.6g of polycarbonate with aluminum trichloride immobilized were charged into a four-necked flask (1000mL) equipped with a mechanical stirrer, a condenser tube, a constant pressure dropping funnel and a thermometer, stirred while being started, reacted at 80 ℃ for 5 hours, cooled to 15 ℃ and filtered to obtain 325.7g of pale yellow liquid ethyl 2-ethoxymethylene-4, 4-difluoroacetoacetate with a content of 35.5% and a yield of 52.1% (based on 4, 4-difluoroacetoacetic acid ethyl ester). In comparative example 1, the fundamental reason for the lower yield is that the polycarbonate catalyst supporting a single metal compound (aluminum trichloride) has a poor catalytic effect and it is difficult to promote the reaction efficiently.
In comparative example 1, the polycarbonate carrying aluminum trichloride was prepared by the following method:
36.2g of tetrahydrofuran (99.5 percent and 0.5mol) is added into a four-mouth bottle (250mL) provided with a mechanical stirring device, a condenser tube, a constant pressure dropping funnel and a thermometer, 13.5g of anhydrous aluminum trichloride (99 percent and 0.1mol) is added under the stirring condition, the mixture is uniformly mixed and heated to reflux, a mixed solution containing 6.8g of aromatic polycarbonate resin and 36.2g of tetrahydrofuran (99.5 percent and 0.5mol) is slowly dropped into the mixture, the dropping is controlled to be finished for 1h, the temperature is kept for 5h, the mixture is cooled to be low, the mixture is filtered, precipitates are respectively washed by tetrahydrofuran and water, and then the precipitates are dried for 10h under the vacuum condition, and 14.5g of polycarbonate fixedly carried with aluminum trichloride is obtained.
Comparative example 2:
a synthetic method of 2-ethoxymethylene-4, 4-difluoroacetoacetic acid ethyl ester comprises the following steps:
169.5g of 4, 4-difluoroacetoacetic acid ethyl ester (98%, 1.0mol) and 157.2g of triethyl orthoformate (99%, 1.05mol) were put into a four-necked flask (1000mL) equipped with a mechanical stirrer, a condenser tube, a constant pressure dropping funnel and a thermometer, stirred, reacted at 80 ℃ for 5 hours, cooled to 15 ℃ and filtered to obtain 326.3g of pale yellow liquid ethyl 2-ethoxymethylene-4, 4-difluoroacetoacetate with a content of 8.7% and a yield of 12.9% (based on the ethyl 4, 4-difluoroacetoacetate).
From the above examples, it can be seen that, compared with the polycarbonate catalyst immobilized with a single metal compound, in the polycarbonate catalyst immobilized with a composite metal compound of the present invention, an unsaturated pi bond in a polycarbonate skeleton can form a stable coordination structure with the composite metal compound, and has higher catalytic activity and use stability, so when the polycarbonate catalyst immobilized with the composite metal compound is used for catalytic synthesis of ethyl 2-ethoxymethylene-4, 4-difluoroacetoacetate, the improvement of reaction yield and reaction rate are facilitated, and the reaction solution is easily separated after the reaction is completed, the operation process is simplified, and at the same time, acetic anhydride is not required to be used as a solvent, the consumption of triethyl orthoformate as a raw material can be reduced, side reactions are less, the production cost is greatly reduced, the content of impurities is reduced, and desolventization treatment is not required after the reaction is completed, the target product can be obtained after the catalyst is removed by filtration, the production efficiency is improved, the recovery and the reuse of the catalyst are realized, and meanwhile, the influence of corrosion on equipment caused by the use of acetic anhydride can be avoided. The synthetic method of the 2-ethoxymethylene-4, 4-difluoroacetoacetic acid ethyl ester has the advantages of simple process, convenient operation, lower cost, no solvent, high reaction rate, high yield and the like, is suitable for large-scale preparation, is beneficial to industrial application, and has high use value and good application prospect. Meanwhile, the polycarbonate catalyst of the adopted immobilized composite metal compound has good stability of the effective components, and the filtered catalyst can be recycled for many times, so that the utilization efficiency of the catalyst is improved, the cost is saved, and the method has high industrial application value.
The above examples are merely preferred embodiments of the present invention, and the scope of the present invention is not limited to the above examples. All technical schemes belonging to the idea of the invention belong to the protection scope of the invention. It should be noted that modifications and embellishments within the scope of the invention may be made by those skilled in the art without departing from the principle of the invention, and such modifications and embellishments should also be considered as within the scope of the invention.
Claims (10)
1. A synthetic method of 2-ethoxymethylene-4, 4-difluoroacetoacetic acid ethyl ester is characterized in that 4, 4-difluoroacetoacetic acid ethyl ester and triethyl orthoformate are used as raw materials, and the 2-ethoxymethylene-4, 4-difluoroacetoacetic acid ethyl ester is synthesized under the action of a polycarbonate catalyst of an immobilized composite metal compound; the polycarbonate catalyst for immobilizing the composite metal compound comprises polycarbonate and the composite metal compound immobilized on the polycarbonate, wherein the composite metal compound comprises two or three of aluminum trichloride, titanium tetrachloride and tin tetrachloride.
2. The synthesis method according to claim 1, wherein the polycarbonate catalyst carrying the composite metal compound is prepared by the following method: adding the composite metal compound into an organic solvent, stirring, heating to reflux, dropwise adding a mixed solution of polycarbonate and the organic solvent, carrying out heat preservation reaction after dropwise adding is finished, and obtaining the polycarbonate catalyst for immobilized composite metal compound after cooling, filtering, washing and drying.
3. The synthesis method according to claim 2, wherein the mass ratio of the composite metal compound to the polycarbonate is 2-3: 1.0; the molar ratio of each component in the composite metal compound is 1:1 or 1:1: 1; the organic solvent is any one of tetrahydrofuran, carbon tetrachloride and trichloroethylene; the polycarbonate is an aromatic polycarbonate resin.
4. The synthesis method according to claim 2, wherein the mixed solution of the polycarbonate and the organic solvent is added dropwise over 1 to 3 hours.
5. The synthesis method according to claim 2, wherein the time of the heat preservation reaction is 2-5 h; the drying is carried out under vacuum conditions; the drying time is 5-10 h.
6. A synthesis process according to any one of claims 1 to 5, characterized by comprising the following steps: mixing 4, 4-difluoro ethyl acetoacetate and triethyl orthoformate with a polycarbonate catalyst of an immobilized composite metal compound for synthetic reaction, and filtering to obtain 2-ethoxy methylene-4, 4-difluoro ethyl acetoacetate.
7. The synthesis method according to claim 6, wherein the mass ratio of the ethyl 4, 4-difluoroacetoacetate to the polycarbonate catalyst supporting the composite metal compound is 1.0: 0.05-0.2.
8. A synthesis method according to claim 7, characterized in that the molar ratio of ethyl 4, 4-difluoroacetoacetate to triethyl orthoformate is 1.0: 1.05-1.5.
9. The synthesis method according to claim 8, characterized in that the synthesis reaction is carried out at a temperature of 80 ℃ to 110 ℃; the time of the synthesis reaction is 1-5 h.
10. The method of synthesizing as claimed in claim 6 wherein after said filtering is completed further comprising: and continuously using the polycarbonate catalyst of the solid-supported composite metal compound obtained after filtration for synthesizing 2-ethoxymethylene-4, 4-difluoroacetoacetic acid ethyl ester.
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| CN104324739A (en) * | 2014-09-19 | 2015-02-04 | 东营海纳新材料有限公司 | Catalyst for synthesis of difluoro ethyl acetoacetate and preparation method thereof |
| US20150158808A1 (en) * | 2013-12-09 | 2015-06-11 | KingChem LLC. | A process for the preparation of alkyl 3-difluoromethyl-1-methyl-1h-pyrazole-4-carboxylate and its analogs |
| CN107501182A (en) * | 2017-07-10 | 2017-12-22 | 中国农业大学 | The trifluoromethyl of 1 substituted-phenyl 5（Difluoromethyl）4 pyrazole carboxylic acid synthetic methods |
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| US20150158808A1 (en) * | 2013-12-09 | 2015-06-11 | KingChem LLC. | A process for the preparation of alkyl 3-difluoromethyl-1-methyl-1h-pyrazole-4-carboxylate and its analogs |
| CN104324739A (en) * | 2014-09-19 | 2015-02-04 | 东营海纳新材料有限公司 | Catalyst for synthesis of difluoro ethyl acetoacetate and preparation method thereof |
| CN107501182A (en) * | 2017-07-10 | 2017-12-22 | 中国农业大学 | The trifluoromethyl of 1 substituted-phenyl 5（Difluoromethyl）4 pyrazole carboxylic acid synthetic methods |
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