CN111686817B - Copper-supported catalyst, preparation method and application thereof - Google Patents
Copper-supported catalyst, preparation method and application thereof Download PDFInfo
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- CN111686817B CN111686817B CN201910192064.9A CN201910192064A CN111686817B CN 111686817 B CN111686817 B CN 111686817B CN 201910192064 A CN201910192064 A CN 201910192064A CN 111686817 B CN111686817 B CN 111686817B
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- alkyl
- copper
- reaction
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- 239000003054 catalyst Substances 0.000 title claims abstract description 78
- 238000002360 preparation method Methods 0.000 title claims abstract description 38
- 150000001875 compounds Chemical class 0.000 claims abstract description 71
- 229920005989 resin Polymers 0.000 claims abstract description 28
- 239000011347 resin Substances 0.000 claims abstract description 28
- 125000003396 thiol group Chemical group [H]S* 0.000 claims abstract description 25
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims abstract description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 23
- 238000000034 method Methods 0.000 claims abstract description 21
- 239000003513 alkali Substances 0.000 claims abstract description 18
- 239000003960 organic solvent Substances 0.000 claims abstract description 16
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 claims abstract description 15
- 239000003446 ligand Substances 0.000 claims abstract description 15
- 229920005990 polystyrene resin Polymers 0.000 claims abstract description 15
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims abstract description 12
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 claims abstract description 12
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims abstract description 6
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims abstract 2
- 238000006243 chemical reaction Methods 0.000 claims description 68
- 125000000217 alkyl group Chemical group 0.000 claims description 48
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 46
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 32
- 239000010949 copper Substances 0.000 claims description 30
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 23
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 18
- 229910052736 halogen Inorganic materials 0.000 claims description 17
- 150000002367 halogens Chemical class 0.000 claims description 17
- 238000004519 manufacturing process Methods 0.000 claims description 17
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 17
- 239000002904 solvent Substances 0.000 claims description 17
- 125000003545 alkoxy group Chemical group 0.000 claims description 16
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical group [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 15
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 claims description 15
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 14
- 229910052802 copper Inorganic materials 0.000 claims description 14
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 13
- 125000003118 aryl group Chemical group 0.000 claims description 13
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical group [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 12
- 239000002585 base Substances 0.000 claims description 12
- 239000000460 chlorine Substances 0.000 claims description 12
- 230000035484 reaction time Effects 0.000 claims description 12
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 12
- 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 12
- 239000004094 surface-active agent Substances 0.000 claims description 11
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 10
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 10
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 10
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims description 9
- 229910021595 Copper(I) iodide Inorganic materials 0.000 claims description 8
- 229910052801 chlorine Inorganic materials 0.000 claims description 8
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 claims description 8
- 239000007789 gas Substances 0.000 claims description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims description 7
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 6
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 6
- 229910052794 bromium Inorganic materials 0.000 claims description 6
- 239000011737 fluorine Substances 0.000 claims description 6
- 229910052731 fluorine Inorganic materials 0.000 claims description 6
- 239000011630 iodine Chemical group 0.000 claims description 6
- 229910052740 iodine Chemical group 0.000 claims description 6
- 238000011084 recovery Methods 0.000 claims description 6
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 6
- 150000001408 amides Chemical group 0.000 claims description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical group C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 4
- 229910019142 PO4 Inorganic materials 0.000 claims description 4
- 239000002202 Polyethylene glycol Substances 0.000 claims description 4
- 229910052783 alkali metal Inorganic materials 0.000 claims description 4
- 150000001340 alkali metals Chemical group 0.000 claims description 4
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 4
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 4
- 238000005859 coupling reaction Methods 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 150000002431 hydrogen Chemical class 0.000 claims description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 4
- 239000010452 phosphate Substances 0.000 claims description 4
- 229920001223 polyethylene glycol Polymers 0.000 claims description 4
- 230000001681 protective effect Effects 0.000 claims description 4
- 229910052708 sodium Inorganic materials 0.000 claims description 4
- 239000011734 sodium Substances 0.000 claims description 4
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 claims description 4
- NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 claims description 4
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 claims description 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
- WGOBPPNNYVSJTE-UHFFFAOYSA-N 1-diphenylphosphanylpropan-2-yl(diphenyl)phosphane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)C(C)CP(C=1C=CC=CC=1)C1=CC=CC=C1 WGOBPPNNYVSJTE-UHFFFAOYSA-N 0.000 claims description 2
- 229910021589 Copper(I) bromide Inorganic materials 0.000 claims description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical group [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 2
- 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 claims description 2
- 229910052786 argon Inorganic materials 0.000 claims description 2
- BERDEBHAJNAUOM-UHFFFAOYSA-N copper(I) oxide Inorganic materials [Cu]O[Cu] BERDEBHAJNAUOM-UHFFFAOYSA-N 0.000 claims description 2
- NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 claims description 2
- 229940112669 cuprous oxide Drugs 0.000 claims description 2
- KRFJLUBVMFXRPN-UHFFFAOYSA-N cuprous oxide Chemical compound [O-2].[Cu+].[Cu+] KRFJLUBVMFXRPN-UHFFFAOYSA-N 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- -1 methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy Chemical group 0.000 claims description 2
- 125000001624 naphthyl group Chemical group 0.000 claims description 2
- 150000002825 nitriles Chemical class 0.000 claims description 2
- 229910052700 potassium Inorganic materials 0.000 claims description 2
- 239000011591 potassium Substances 0.000 claims description 2
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical group [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 2
- 239000001488 sodium phosphate Substances 0.000 claims description 2
- 229910000162 sodium phosphate Inorganic materials 0.000 claims description 2
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical group [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 claims description 2
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 1
- 125000005915 C6-C14 aryl group Chemical group 0.000 claims 1
- 238000003477 Sonogashira cross-coupling reaction Methods 0.000 abstract description 10
- 231100000419 toxicity Toxicity 0.000 abstract description 4
- 230000001988 toxicity Effects 0.000 abstract description 4
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 41
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
- UEXCJVNBTNXOEH-UHFFFAOYSA-N Ethynylbenzene Chemical group C#CC1=CC=CC=C1 UEXCJVNBTNXOEH-UHFFFAOYSA-N 0.000 description 20
- 239000000706 filtrate Substances 0.000 description 20
- 239000012044 organic layer Substances 0.000 description 20
- 239000000047 product Substances 0.000 description 17
- 239000000203 mixture Substances 0.000 description 15
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 14
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
- 238000004440 column chromatography Methods 0.000 description 11
- 239000000741 silica gel Substances 0.000 description 11
- 229910002027 silica gel Inorganic materials 0.000 description 11
- 230000015572 biosynthetic process Effects 0.000 description 10
- 239000012043 crude product Substances 0.000 description 10
- 239000003480 eluent Substances 0.000 description 10
- 239000003208 petroleum Substances 0.000 description 10
- 238000003756 stirring Methods 0.000 description 10
- 238000003786 synthesis reaction Methods 0.000 description 10
- 229910052763 palladium Inorganic materials 0.000 description 7
- SYSZENVIJHPFNL-UHFFFAOYSA-N (alpha-D-mannosyl)7-beta-D-mannosyl-diacetylchitobiosyl-L-asparagine, isoform B (protein) Chemical compound COC1=CC=C(I)C=C1 SYSZENVIJHPFNL-UHFFFAOYSA-N 0.000 description 5
- 239000012065 filter cake Substances 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
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- 238000001035 drying Methods 0.000 description 4
- 229910052751 metal Inorganic materials 0.000 description 4
- 239000002184 metal Substances 0.000 description 4
- 239000003444 phase transfer catalyst Substances 0.000 description 4
- 239000011949 solid catalyst Substances 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 229910001385 heavy metal Inorganic materials 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 238000001095 inductively coupled plasma mass spectrometry Methods 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 3
- BXXYBNVPUWTQFR-UHFFFAOYSA-N 1-methoxy-4-(2-phenylethynyl)benzene Chemical compound C1=CC(OC)=CC=C1C#CC1=CC=CC=C1 BXXYBNVPUWTQFR-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 2
- 239000012295 chemical reaction liquid Substances 0.000 description 2
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- 238000010626 work up procedure Methods 0.000 description 2
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- RGSINQHSYQBZBN-UHFFFAOYSA-N 1-(2-phenylethynyl)-2-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC=C1C#CC1=CC=CC=C1 RGSINQHSYQBZBN-UHFFFAOYSA-N 0.000 description 1
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- IUGPZGPRLHJZAW-UHFFFAOYSA-N 1-chloro-2-(2-phenylethynyl)benzene Chemical compound ClC1=CC=CC=C1C#CC1=CC=CC=C1 IUGPZGPRLHJZAW-UHFFFAOYSA-N 0.000 description 1
- GWQSENYKCGJTRI-UHFFFAOYSA-N 1-chloro-4-iodobenzene Chemical compound ClC1=CC=C(I)C=C1 GWQSENYKCGJTRI-UHFFFAOYSA-N 0.000 description 1
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- GDVKFRBCXAPAQJ-UHFFFAOYSA-A dialuminum;hexamagnesium;carbonate;hexadecahydroxide Chemical compound [OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Al+3].[Al+3].[O-]C([O-])=O GDVKFRBCXAPAQJ-UHFFFAOYSA-A 0.000 description 1
- HNPSIPDUKPIQMN-UHFFFAOYSA-N dioxosilane;oxo(oxoalumanyloxy)alumane Chemical compound O=[Si]=O.O=[Al]O[Al]=O HNPSIPDUKPIQMN-UHFFFAOYSA-N 0.000 description 1
- GPAYUJZHTULNBE-UHFFFAOYSA-N diphenylphosphine Chemical compound C=1C=CC=CC=1PC1=CC=CC=C1 GPAYUJZHTULNBE-UHFFFAOYSA-N 0.000 description 1
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- 239000000463 material Substances 0.000 description 1
- 239000008204 material by function Substances 0.000 description 1
- TZIHFWKZFHZASV-UHFFFAOYSA-N methyl formate Chemical compound COC=O TZIHFWKZFHZASV-UHFFFAOYSA-N 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000002791 soaking Methods 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 239000002351 wastewater Substances 0.000 description 1
- 239000010457 zeolite Substances 0.000 description 1
Classifications
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- 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
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/24—Phosphines, i.e. phosphorus bonded to only carbon atoms, or to both carbon and hydrogen atoms, including e.g. sp2-hybridised phosphorus compounds such as phosphabenzene, phosphole or anionic phospholide ligands
- B01J31/2404—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C15/00—Cyclic hydrocarbons containing only six-membered aromatic rings as cyclic parts
- C07C15/40—Cyclic hydrocarbons containing only six-membered aromatic rings as cyclic parts substituted by unsaturated carbon radicals
- C07C15/50—Cyclic hydrocarbons containing only six-membered aromatic rings as cyclic parts substituted by unsaturated carbon radicals polycyclic non-condensed
- C07C15/54—Cyclic hydrocarbons containing only six-membered aromatic rings as cyclic parts substituted by unsaturated carbon radicals polycyclic non-condensed containing a group with formula
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
- C07C205/06—Compounds containing nitro groups bound to a carbon skeleton having nitro groups bound to carbon atoms of six-membered aromatic rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C22/00—Cyclic compounds containing halogen atoms bound to an acyclic carbon atom
- C07C22/02—Cyclic compounds containing halogen atoms bound to an acyclic carbon atom having unsaturation in the rings
- C07C22/04—Cyclic compounds containing halogen atoms bound to an acyclic carbon atom having unsaturation in the rings containing six-membered aromatic rings
- C07C22/08—Cyclic compounds containing halogen atoms bound to an acyclic carbon atom having unsaturation in the rings containing six-membered aromatic rings containing fluorine
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C25/00—Compounds containing at least one halogen atom bound to a six-membered aromatic ring
- C07C25/24—Halogenated aromatic hydrocarbons with unsaturated side chains
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C43/00—Ethers; Compounds having groups, groups or groups
- C07C43/02—Ethers
- C07C43/20—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring
- C07C43/215—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring having unsaturation outside the six-membered aromatic rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
- C07C49/76—Ketones containing a keto group bound to a six-membered aromatic ring
- C07C49/794—Ketones containing a keto group bound to a six-membered aromatic ring having unsaturation outside an aromatic ring
- C07C49/796—Ketones containing a keto group bound to a six-membered aromatic ring having unsaturation outside an aromatic ring polycyclic
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2531/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- C07C2531/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- C07C2531/24—Phosphines
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Abstract
The invention discloses a copper-supported catalyst, a preparation method and application thereof. The invention discloses a preparation method of a copper-supported catalyst, which comprises the following steps: in an organic solvent, under the action of alkali, a Cu (I) compound, sulfhydryl resin and phosphine ligand react to obtain the catalyst; wherein the mercapto resin is prepared by a process comprising the step of reacting chloromethyl polystyrene resin with thiourea. The copper-supported catalyst is low in cost and low in toxicity, can be used in a water phase, and can realize the greening of the Sonogashira reaction.
Description
Technical Field
The invention relates to a copper-supported catalyst, a preparation method and application thereof.
Background
The coupling reaction between palladium and copper catalyzed aryl halides and terminal alkynes, namely the Sonogashira reaction, has very wide application in the synthesis of novel functional materials, pesticides, medicines and nano-molecular devices. However, the conventional Sonogashira reaction has some remarkable disadvantages in practical application, such as using an expensive homogeneous palladium catalyst, difficult catalyst recovery, easy environmental pollution caused by heavy metal-containing wastewater, and product pollution caused by heavy metals remained in the product. In the pharmaceutical industry, how to efficiently reduce heavy metal residues in products is a problem that such reactions cause headache to numerous pharmaceutical developers in production applications. In addition, the common solvents for the coupling reaction are organic solvents such as tetrahydrofuran, acetonitrile and the like. Most of the solvents are toxic, volatile, inflammable and difficult to recycle, and when used in a large amount, the solvents have great potential safety hazards and environmental risks.
The supported metal catalyst is prepared by supporting metal catalyst on carrier such as silica gel, zeolite, high molecular polymer, etc., and through stable and dispersed catalyst, the stability of catalyst is improved, and the micro environment of catalyst is improved, so as to influence and improve the catalytic performance of catalyst. Meanwhile, the supported metal catalyst can separate the catalyst and the reaction liquid through simple filtering operation, and has the advantages of simple recovery, low metal residue in the product and the like compared with a homogeneous catalyst. There have been many reports on a supported palladium catalyst applicable to the Sonogashira reaction, for example, CN101678330 reports on a macroporous resin carrier supported palladium catalyst applicable to the Sonogashira reaction, CN104277079a reports on a palladium-lanthanum coordination polymer catalyst applicable to the Sonogashira reaction, and CN106179333a reports on a hydrotalcite supported palladium catalyst applicable to the Sonogashira reaction.
Compared with palladium catalyst, copper catalyst has the characteristics of low price, lower toxicity, more environment-friendly property and the like. The use of water as a solvent can significantly reduce the safety risks and the risk of atmospheric pollution associated with the use of a large amount of volatile organic solvents. Therefore, the development of a supported copper catalyst that can be used in the Sonogashira reaction in aqueous media is of great importance for the greening of the chemical industry.
Disclosure of Invention
The invention aims to overcome the defects of high toxicity and high price of a palladium catalyst applied to a Sonogashira reaction in the prior art, and provides a copper-supported catalyst, a preparation method and application thereof. The copper-supported catalyst is low in cost and low in toxicity, can be used in a water phase, and can realize the greening of the Sonogashira reaction.
The invention mainly solves the technical problems through the following technical scheme.
The invention provides a preparation method of a copper-supported catalyst, which comprises the following steps: in an organic solvent, under the action of alkali, a Cu (I) compound, sulfhydryl resin and phosphine ligand react to obtain the catalyst; wherein the mercapto resin is prepared by a process comprising the step of reacting chloromethyl polystyrene resin with thiourea.
The chloromethyl polystyrene resin is preferably 100 to 500 mesh in size, and more preferably 100 to 200 mesh in size. The Cl content in the chloromethyl polystyrene resin is preferably 0.1 to 3mmol/g, more preferably 0.8 to 1.2mmol/g (e.g., 1 mmol/g).
In the preparation method of the copper-supported catalyst, the organic solvent can be an organic solvent which is conventional in the reaction in the field, and particularly preferably an amide solvent and/or a nitrile solvent. The amide solvent is preferably one or more of N, N-dimethylacetamide, N-dimethylformamide and N-methylpyrrolidone, and more preferably N, N-dimethylformamide.
In the preparation method of the copper-supported catalyst, the Cu (I) compound can be Cu (I) compound conventional in the field, and the copper-supported catalyst is particularly preferably one or more of cuprous bromide, cuprous iodide and cuprous oxide, and more preferably cuprous iodide.
In the preparation method of the copper-supported catalyst, the molar concentration of the Cu (I) compound in the organic solvent may be a molar concentration which is conventional in such a reaction in the art, and the present invention is particularly preferably 0.01 to 1mol/L, and further preferably 0.1 to 0.2mol/L (e.g., 2/15 mol/L).
In the preparation method of the copper-supported catalyst, the phosphine ligand can be phosphine ligand conventional in the art, and the phosphine ligand is preferably one or more of 1, 10-phenanthroline, triphenylphosphine, 1' -bis-diphenylphosphino ferrocene and 1, 2-bis (diphenylphosphino) propane, and more preferably triphenylphosphine.
In the preparation method of the copper-supported catalyst, the molar ratio of the phosphine ligand to the Cu (I) compound may be a molar ratio which is conventional in this type of reaction in the art, and the present invention is particularly preferably 5:1 to 1:1, and further preferably 4:1 to 1:1 (e.g., 3:1).
In the preparation of the copper-supported catalyst, the base may be a base conventional in the art, and particularly preferably one or more of hydroxide, carbonate, phosphate, MCN and R ' OM ' in which M is an alkali metal and R ' is C 1-4 Alkyl, M' is an alkali metal; the base is further preferably a carbonate. The hydroxide is preferably potassium hydroxide. The carbonate is preferably one or more of potassium carbonate, sodium carbonate and cesium carbonate, more preferably potassium carbonate and/or sodium carbonate, and most preferably potassium carbonate. The phosphate is preferably sodium phosphate. Preferably, M is sodium. The R' group is preferably methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or tert-butyl, most preferably tert-butyl. Preferably, M' is potassium or sodium. The R 'OM' is preferably potassium tert-butoxide or sodium tert-butoxide.
In the preparation method of the copper-supported catalyst, the molar ratio of the base to the Cu (I) compound may be a molar ratio conventional in such reactions in the art, and the present invention is particularly preferably 5:1 to 1:5, and further preferably 2:1 to 1:2 (e.g., 1:1).
In the preparation method of the copper-supported catalyst, the mass concentration of the mercapto resin in the organic solvent may be a mass concentration conventional in such reactions in the art, and the present invention is particularly preferably 0.01 to 1g/mL, and further preferably 0.05 to 0.08g/mL (e.g., 1/15 g/mL).
In the preparation method of the copper-supported catalyst, the reaction time of the reaction may be a reaction time conventional in the art, and the present invention is preferably 2 to 30 hours, more preferably 12 to 20 hours (for example, 16 hours).
In the preparation method of the copper-supported catalyst, the reaction temperature of the reaction may be a reaction temperature which is conventional in the art of such a reaction, and the present invention is particularly preferably 50 to 110 ℃, further preferably 70 to 90 ℃ (e.g., 85 ℃).
In a preferred embodiment of the present invention, the method for preparing the copper-supported catalyst comprises the steps of: mixing the Cu (I) compound, the phosphine ligand and the organic solvent, and then adding the alkali and the sulfhydryl resin for reaction.
In a preferred embodiment of the present invention, the method for preparing a copper-supported catalyst may further comprise a post-treatment step after the completion of the reaction. The work-up steps are conventional in the art, filtration, washing and drying being particularly preferred according to the invention. The reagent used for the washing is the organic solvent. The drying means may be conventional in the art (e.g., suction).
The preparation method of the sulfhydryl resin can be conventional in the field, and preferably comprises the following steps: mixing chloromethyl polystyrene resin, thiourea, a phase transfer catalyst and a solvent, and then carrying out a salifying reaction to obtain a product A; and carrying out hydrolysis reaction on the product A under the action of alkali to obtain the sulfhydryl resin. Specific preparation methods can be referred to in the literature: chen Yi, warrior, wu Xiaobin, polymer communications, 1985,5, 355; wang Naidong, synthesis and Performance studies of thiol resins, ion exchange and adsorption, 1988, 19-23.
In the preparation method of the mercapto resin, the solvent can be a solvent which is conventional in the reaction in the field, and water is particularly preferred in the invention.
In the preparation method of the mercapto resin, the concentration of the chloromethyl polystyrene resin in the solvent can be a concentration conventional in the art for such reactions, and the concentration is particularly preferably 0.1 to 1g/mL (e.g., 5/18 g/mL).
In the preparation method of the mercapto resin, the mass ratio of the thiourea to the chloromethyl polystyrene resin can be the mass ratio which is conventional in the reaction in the field, and the mass ratio is particularly preferably 0.01:1 to 1:1, and more preferably 0.01:1 to 0.2:1 (for example, 0.1:1).
In the preparation method of the sulfhydryl resin, the phase transfer catalyst can be a conventional phase transfer catalyst for reactions of the type in the field, and tetrabutylammonium bromide is particularly preferred in the invention.
In the preparation method of the mercapto resin, the mass ratio of the phase transfer catalyst to the chloromethyl polystyrene resin may be a mass ratio which is conventional in the art, and the mass ratio is particularly preferably 0.001:1 to 1:0.1, and more preferably 0.001:1 to 0.02:1 (e.g., 0.01:1).
In the method for producing a mercapto resin, the reaction time of the salt-forming reaction may be a reaction time which is conventional in the art, and the reaction time is particularly preferably 10 to 24 hours, and further preferably 14 to 18 hours (for example, 16 hours). The reaction temperature of the salt-forming reaction may be a reaction temperature conventional in this type of reaction in the art, and the present invention is particularly preferably 80 to 120 ℃ (e.g., 100 ℃).
In the preparation method of the sulfhydryl resin, the alkali can be alkali conventional in the reaction in the field, and sodium hydroxide is particularly preferred in the invention.
In the method for producing a mercapto resin, the concentration of the base in the solvent may be a concentration which is conventional in such reactions in the art, and the concentration of the base in the solvent is particularly preferably 0.01 to 0.1g/mL, and more preferably 0.01 to 0.2g/mL (e.g., 333/19000 g/mL).
In the method for producing a mercapto resin, the reaction time of the hydrolysis reaction may be a reaction time which is conventional in the art, and is particularly preferably 8 to 24 hours, and further preferably 8 to 12 hours (e.g., 10 hours). The reaction temperature of the hydrolysis reaction may be a reaction temperature conventional in this type of reaction in the art, and the present invention is particularly preferably 80 to 120 ℃ (e.g., 100 ℃).
The invention also provides a copper-supported catalyst prepared by the preparation method.
The invention also provides a preparation method of the compound shown in the formula I, which comprises the following steps: under the protection gas, in water, under the action of a surfactant, alkali and the copper supported catalyst, the compound shown in the formula II and the compound shown in the formula III are subjected to the coupling reaction shown in the following,
wherein R is 1 、R 2 、R 3 、R 4 And R is 5 Are each independently hydrogen, C 1-8 Alkyl, C 1-8 Alkoxy, nitro, -C (=o) R 3-1 Halogen, or halogen-substituted C 1-8 An alkyl group;
x' is chlorine, bromine or iodine;
R 6 is C 1-8 Alkyl or C 6-20 An aryl group;
R 3-1 is C 1-8 An alkyl group.
In a preferred embodiment of the present invention, R is 1 、R 2 、R 4 And R is 5 Preferably hydrogen, said R 3 Preferably C 1-8 Alkyl, C 1-8 Alkoxy, nitro, -C (=o) R 3-1 Halogen, or halogen-substituted C 1-8 An alkyl group.
In a preferred embodiment of the invention, when R 1 、R 2 、R 3 、R 4 And R is 5 Each independently is C 1-8 In the case of alkyl, said C 1-8 Alkyl is preferably C 1-4 Alkyl is more preferably methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or tert-butyl, most preferably methyl.
In a preferred embodiment of the invention, when R 1 、R 2 、R 3 、R 4 And R is 5 Each independently is C 1-8 In the case of alkoxy, said C 1-8 Alkoxy is preferably C 1-4 Alkoxy is more preferably methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy or tert-butoxy, most preferably methoxy.
In a preferred embodiment of the invention, when R 1 、R 2 、R 3 、R 4 And R is 5 When each is independently halogen, the halogen is preferably fluorine, chlorine, bromine or iodine, most preferably chlorine.
In a preferred embodiment of the invention, when R 1 、R 2 、R 3 、R 4 And R is 5 Each independently halogen substituted C 1-8 In the case of alkyl, the halogen is preferably fluorine, chlorine, bromine or iodine, and more preferably fluorine; the C is 1-8 Alkyl is preferably C 1-4 Alkyl is more preferably methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or tert-butyl, most preferably methyl. Said halogen-substituted C 1-8 The alkyl group is preferably trifluoromethyl.
In a preferred embodiment of the invention, when R 1 、R 2 、R 3 、R 4 And R is 5 Each independently is-C (=O) R 3-1 When said R is 3-1 Preferably C 1-4 Alkyl is more preferably methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or tert-butyl, most preferably methyl.
In a preferred embodiment of the invention, said X' is preferably iodine.
In a preferred embodiment of the invention, when R 6 Is C 1-8 In the case of alkyl, said C 1-8 Alkyl is preferably C 1-4 Alkyl is more preferably methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or tert-butyl.
In a preferred embodiment of the invention, when R 6 Is C 6-20 Aryl, the C 6-20 Aryl is preferably C 6-14 Aryl is further preferably phenyl, naphthyl or anthracenyl, most preferably phenyl.
In a preferred embodiment of the present invention, R is 3 Preferably halogen-substituted C 1-8 Alkyl, C 1-8 Alkyl or C 1-8 An alkoxy group.
In a preferred embodiment of the present invention, R is 6 Preferably C 6-20 Aryl groups.
In a preferred embodiment of the present invention, R is 3 Preferably methyl, methoxy, methanone, nitro, trifluoromethyl or chloro.
In a preferred embodiment of the inventionIn the scheme, R is 6 Phenyl is preferred.
In a preferred embodiment of the present invention, the compound of formula II is preferably any one of the following compounds:
in the process for preparing the compounds of formula I, the protective gas may be any protective gas customary in the art, nitrogen and/or argon are particularly preferred according to the invention, nitrogen being further preferred.
In the process for preparing the compounds of the formula I, the molar concentration of the compounds of the formula II in the water may be a molar concentration customary in this type of reaction, particularly preferably from 0.01 to 1mol/L, more preferably from 0.1 to 0.2mol/L (for example 0.12 mol/L).
In the preparation method of the compound shown in the formula I, the surfactant can be a surfactant conventional in the reaction in the field, and particularly preferably one or more of tetrabutylammonium bromide, tetrabutylammonium chloride, polyethylene glycol and sodium dodecyl sulfate, further preferably tetrabutylammonium bromide and/or polyethylene glycol, and most preferably tetrabutylammonium bromide.
In the process for preparing the compounds of formula I, the molar ratio of the surfactant to the compound of formula II may be in a molar ratio conventional in this type of reaction, and is particularly preferably 1:10 to 10:1, more preferably 1:2 to 2:1 (e.g. 1:1).
In the preparation of the compounds of formula I, the bases may be bases customary in this type of reaction, with particular preference being given to carbonates and/or hydroxides, and more preferably to carbonates. The carbonate is preferably one or more of sodium carbonate, potassium carbonate and/or cesium carbonate, and more preferably potassium carbonate. The hydroxide is preferably sodium hydroxide and/or potassium hydroxide.
In the process for the preparation of the compounds of formula I, the molar ratio of the base to the compound of formula II may be in a molar ratio conventional in the art for such reactions, and is particularly preferably 1:10 to 10:1, more preferably 1:1 to 3:1 (e.g. 2:1).
In the process for preparing the compounds of formula I, the molar ratio of copper in the copper-supported catalyst to the compounds of formula II may be conventional in this type of reaction, and is particularly preferably from 1:200 to 1:5, more preferably from 1:100 to 1:10 (e.g., 1:20).
In the process for preparing the compounds of formula I, the molar ratio of the compounds of formula III to the compounds of formula II may be in a molar ratio conventional in this type of reaction, and is particularly preferably 1:1 to 3:1, more preferably 1:1 to 2:1, still more preferably 1:1 to 1.5:1 (e.g. 1.1:1).
In the preparation of the compounds of formula I, the progress of the reaction may be monitored by conventional monitoring methods in the art (e.g., TLC, HPLC or NMR), typically by monitoring the disappearance of the compounds of formula II or of formula III as the end point of the reaction. The reaction time of the reaction is preferably 10 to 30 hours, more preferably 16 to 20 hours (for example, 16 hours, 18 hours, 20 hours).
In the preparation of the compounds of the formula I, the reaction temperature of the reaction may be conventional in the art, and is particularly preferably from 90 to 130℃and more preferably from 100 to 110 ℃.
In a preferred embodiment of the present invention, the process for preparing a compound of formula I may further comprise recovering the copper-supported catalyst after the reaction. The recovery mode can be conventional in the art, and the copper-supported catalyst is preferably obtained by filtering the reaction liquid after the reaction is finished.
In a preferred embodiment of the present invention, a process for the preparation of a compound of formula I comprises the steps of: mixing the copper-supported catalyst, the surfactant, the alkali, the compound shown in the formula II and the water, stirring at room temperature, adding the compound shown in the formula III, and reacting under the protection gas.
In a preferred embodiment of the present invention, the process for the preparation of the compounds of formula I further comprises a post-treatment step after the reaction has ended. The work-up procedure is conventional in the art, and the invention particularly preferably comprises quenching, filtering, separating, extracting, drying, concentrating and purifying the reaction solution. The reagents used for the quenching may be conventional in the art (e.g., methyl t-butyl ether). The drying agent used for the drying may be conventional in the art (e.g., anhydrous magnesium sulfate). The purification means may be conventional in the art (e.g., column chromatography).
In the present invention, room temperature means 10 to 30 ℃.
The above preferred conditions can be arbitrarily combined on the basis of not deviating from the common knowledge in the art, and thus, each preferred embodiment of the present invention can be obtained.
The reagents and materials used in the present invention are commercially available.
The invention has the positive progress effects that: the copper-supported catalyst of the invention is cheap and low in toxicity, can be used in water phase, and realizes the green reaction.
Detailed Description
The invention is further illustrated by means of the following examples, which are not intended to limit the scope of the invention. The experimental methods, in which specific conditions are not noted in the following examples, were selected according to conventional methods and conditions, or according to the commercial specifications.
In the examples below, room temperature is 10℃to 30 ℃. ICP-MS refers to inductively coupled plasma mass spectrometry. Chloromethyl polystyrene resins were purchased from Tianjin Nankai and technology Co., ltd.
EXAMPLE 1 Synthesis of mercapto resin
In a 500mL round bottom flask, 50g of chloromethyl polystyrene resin (wherein Cl content is 1 mmol/g), 5g of thiourea, 0.5g of tetrabutylammonium bromide and 180mL of water were successively added, and the mixture was heated to 100℃and incubated for 16 hours. After the reaction was completed, the reaction mixture was cooled to room temperature, 3.33g of sodium hydroxide and 10mL of water were added thereto, and the temperature was raised to 100℃to effect a reaction for 12 hours. The reaction mixture was cooled to room temperature, and 5.3g of concentrated sulfuric acid was added dropwise to adjust the pH to 4. Filtering, leaching the filter cake by using 300mL of ethanol, leaching by using 300mL of methyl tertiary butyl ether, and carrying out vacuum drying by using an oil pump to obtain 49g of product.
EXAMPLE 2 Synthesis of copper-Supported catalyst
To a 250mL round bottom flask was added 3.8g (20 mmol) of cuprous iodide, 15.7g (60 mmol) of triphenylphosphine, 150mL of N, N-dimethylformamide, and the mixture was stirred at room temperature for half an hour. Then, 2.8g (20 mmol) of potassium carbonate was added in this order, 10.0g of the mercapto resin obtained in example 1 was heated to 85℃and reacted at a constant temperature for 16 hours. The reaction solution was cooled to room temperature, filtered, and the filter cake was rinsed by soaking in 50mL of N, N-dimethylformamide, and dried by suction to obtain 13.7 g of a solid catalyst. The copper content was 1.8% by ICP-MS detection.
Example 34 Synthesis of (phenylethynyl) anisole
To a 100mL round-bottomed flask was successively added 1.1g (copper content 19.8mg,0.3 mmol) of the copper-supported catalyst prepared in example 2, 1.9g (6 mmol) of tetrabutylammonium bromide, 1.7g (12 mmol) of potassium carbonate, 1.4g (6 mmol) of p-methoxyiodobenzene, 50mL of water, and stirred at room temperature for 5 minutes. Then 0.68g (6.6 mmol) of phenylacetylene was added thereto, and the mixture was refluxed under nitrogen atmosphere for 18 hours. Cooled to room temperature, 50mL of methyl tert-butyl ether was added, and the resulting solid was filtered and used as catalyst directly for the next reaction. The filtrate was poured into a separating funnel and separated, extracted once with 20mL of methyl tert-butyl ether, and the organic layers were combined. The combined organic layers were dried over anhydrous magnesium sulfate, filtered to give a filtrate which was concentrated, and the crude product obtained was purified by column chromatography on silica gel (200-300 mesh) with ethyl acetate/petroleum ether as eluent to give the desired product in 93% yield.
Example 4 recovery and reuse of catalyst
To a 100mL round-bottomed flask, 0.6g (0.17 mmol) of the copper-supported catalyst recovered in example 3, 0.95g (3 mmol) of tetrabutylammonium bromide, 0.85g (6 mmol) of potassium carbonate, 0.7g (3 mmol) of p-methoxyiodobenzene, 25mL of water were successively added, and the mixture was stirred at room temperature for 5 minutes. Then, 0.34g (3.3 mmol) of phenylacetylene was added thereto, and the mixture was refluxed under nitrogen atmosphere for 20 hours. 50mL of methyl tertiary butyl ether was added and filtered, and the resulting solid was used as a catalyst and was used directly for the next reaction. The filtrate was poured into a separatory funnel and extracted once again with 20mL of methyl tert-butyl ether, and the organic layers were combined. The combined organic layers were dried over anhydrous magnesium sulfate, filtered to give a filtrate which was concentrated, and the crude product obtained was purified by column chromatography on silica gel (200-300 mesh) with ethyl acetate/petroleum ether as eluent to give the desired product in 87% yield.
Example 5 4 Synthesis of (phenylethynyl) toluene
To a 100mL round-bottomed flask was successively added 1.1g (copper content 19.8mg,0.3 mmol) of the copper-supported catalyst prepared in example 2, 1.9g of tetrabutylammonium bromide, 1.70g (12 mmol) of potassium carbonate, 1.3g (6 mmol) of p-methyliodide, 50mL of water and stirring at room temperature for 5 minutes. Then, 0.68g (6.6 mmol) of phenylacetylene was added thereto, and the mixture was refluxed under stirring under a nitrogen ball for 16 hours. Cooled to room temperature, 50mL of methyl tert-butyl ether was added, filtered, the filtrate was poured into a separating funnel, extracted once again with 20mL of methyl tert-butyl ether, and the organic layers were combined. The combined organic layers were dried over anhydrous magnesium sulfate, filtered to give a filtrate which was concentrated, and the crude product obtained was purified by column chromatography on silica gel (200-300 mesh) with ethyl acetate/petroleum ether as eluent to give the desired product in 92% yield.
Example 6 4 Synthesis of (phenylethynyl) acetophenone
To a 100mL round-bottomed flask was successively added 1.1g (copper content 19.8mg,0.3 mmol) of the copper-supported catalyst prepared in example 2, 1.9g (6 mmol) of tetrabutylammonium bromide, 1.7g (12 mmol) of potassium carbonate, 1.48g (6 mmol) of p-iodoacetophenone, 50mL of water, and stirring at room temperature for 5 minutes. Then, 0.68g (6.6 mmol) of phenylacetylene was added thereto, and the mixture was refluxed under stirring under a nitrogen ball for 18 hours. Cooled to room temperature, 50mL of methyl tert-butyl ether was added, filtered, the filtrate was poured into a separating funnel, extracted once again with 20mL of methyl tert-butyl ether, and the organic layers were combined. The combined organic layers were dried over anhydrous magnesium sulfate, filtered to give a filtrate which was concentrated, and the crude product obtained was purified by column chromatography on silica gel (200-300 mesh) with ethyl acetate/petroleum ether as eluent to give the desired product in 86% yield.
Example 7 4 Synthesis of (phenylethynyl) nitrobenzene
To a 100mL round-bottomed flask was successively added 1.1g (copper content 19.8mg,0.3 mmol) of the copper-supported catalyst prepared in example 2, 1.9g (6 mmol) of tetrabutylammonium bromide, 1.7g (12 mmol) of potassium carbonate, 1.5g (6 mmol) of p-iodonitrobenzene, 50mL of water and stirring at room temperature for 5 minutes. Phenylacetylene 0.68 (6.6 mmol) was then added and the mixture was refluxed under nitrogen for 18 hours. Cooled to room temperature, 50mL of methyl tert-butyl ether was added, filtered, the filtrate was poured into a separating funnel, extracted once again with 20mL of methyl tert-butyl ether, and the organic layers were combined. The combined organic layers were dried over anhydrous magnesium sulfate, filtered to give a filtrate which was concentrated, and the crude product obtained was purified by column chromatography on silica gel (200-300 mesh) with ethyl acetate/petroleum ether as eluent to give the desired product in 81% yield.
Example 8 4 Synthesis of (phenylethynyl) benzotrifluoride
To a 100mL round-bottomed flask, 1.1g (copper content 19.8mg,0.3 mmol) of the copper-supported catalyst prepared in example 2, 1.9g (6 mmol) of tetrabutylammonium bromide, 1.7g (12 mmol) of potassium carbonate, 1.65g (6 mmol) of p-trifluoromethylidine, 50mL of water and stirring at room temperature for 5 minutes were successively added. Then, 0.68g (6.6 mmol) of phenylacetylene was added thereto, and the mixture was refluxed under stirring under a nitrogen ball for 16 hours. Cooled to room temperature, 50mL of methyl tert-butyl ether was added, filtered, the filtrate was poured into a separating funnel, extracted once again with 20mL of methyl tert-butyl ether, and the organic layers were combined. The combined organic layers were dried over anhydrous magnesium sulfate, filtered to give a filtrate which was concentrated, and the crude product obtained was purified by column chromatography on silica gel (200-300 mesh) with ethyl acetate/petroleum ether as eluent to give the desired product in 91% yield.
Example 9 4 Synthesis of (phenylethynyl) chlorobenzene
To a 100mL round-bottomed flask was successively added 1.1g (copper content 19.8mg,0.3 mmol) of the copper-supported catalyst prepared in example 2, 1.9g (6 mmol) of tetrabutylammonium bromide, 1.7g (12 mmol) of potassium carbonate, 1.44g (6 mmol) of p-chloroiodobenzene, 50mL of water and stirring at room temperature for 5 minutes. Then, 0.68g (6.6 mmol) of phenylacetylene was added thereto, and the mixture was refluxed under stirring under a nitrogen ball for 16 hours. Cooled to room temperature, 50mL of methyl tert-butyl ether was added, filtered, the filtrate was poured into a separating funnel, extracted once again with 20mL of methyl tert-butyl ether, and the organic layers were combined. The combined organic layers were dried over anhydrous magnesium sulfate, filtered to give a filtrate which was concentrated, and the crude product obtained was purified by column chromatography on silica gel (200-300 mesh) with ethyl acetate/petroleum ether as eluent to give the desired product in 75% yield.
Example 10
In a 250mL round bottom flask was added 0.76g (4 mmol) of cuprous iodide, ligand (12 mmol), 30mL of N, N-dimethylformamide, and stirred at room temperature for half an hour. Then, 0.56g (4 mmol) of potassium carbonate was added in this order, 2.0g of the mercapto resin obtained in example 1 was heated to 85℃and reacted at a constant temperature for 16 hours. The reaction solution was cooled to room temperature, filtered, and the filter cake was rinsed with 10mL of N, N-dimethylformamide, and dried by suction to obtain a solid catalyst.
To a 100mL round-bottomed flask was added, in order, 1.9g (6 mmol) of the prepared copper-supported catalyst (0.3 mmol), 1.7g (12 mmol) of potassium carbonate, 1.4g (6 mmol) of p-methoxyiodobenzene, 50mL of water, and stirred at room temperature for 5 minutes. Then 0.68g (6.6 mmol) of phenylacetylene was added thereto, and the mixture was refluxed under nitrogen atmosphere for 18 hours. Cooled to room temperature, 50mL of methyl tert-butyl ether was added, filtered, the filtrate was poured into a separating funnel, and extracted once with 20mL of methyl tert-butyl ether, and the organic layers were combined. The combined organic layers were dried over anhydrous magnesium sulfate, filtered to give a filtrate, which was concentrated, and the crude product obtained was purified by column chromatography on silica gel (200-300 mesh) with ethyl acetate/petroleum ether as eluent to give the desired product.
TABLE 1 yields of 4- (phenylethynyl) anisole with different ligands
| Numbering device | Ligand | Yield% |
| 1 | 1, 10-phenanthroline | 29 |
| 2 | 1,1' -bis (diphenylphosphine) ferrocene | 91 |
Example 11
To a 250mL round bottom flask was added 0.76g (4 mmol) of cuprous iodide, 3.14g (12 mmol) of triphenylphosphine, 30mL of N, N-dimethylformamide, and the mixture was stirred at room temperature for half an hour. Then, 2.0g of the mercapto resin prepared in example 1 was added successively with a base (4 mmol), heated to 85℃and reacted at a constant temperature for 16 hours. The reaction solution was cooled to room temperature, filtered, and the filter cake was rinsed with 10mL of N, N-dimethylformamide, and dried by suction to obtain a solid catalyst.
To a 100mL round-bottomed flask was added, in order, 1.9g (6 mmol) of the prepared copper-supported catalyst (0.3 mmol), 1.7g (12 mmol) of potassium carbonate, 1.4g (6 mmol) of p-methoxyiodobenzene, 50mL of water, and stirred at room temperature for 5 minutes. Then 0.68g (6.6 mmol) of phenylacetylene was added thereto, and the mixture was refluxed under nitrogen atmosphere for 18 hours. Cooled to room temperature, 50mL of methyl tert-butyl ether was added, filtered, the filtrate was poured into a separating funnel, and extracted once with 20mL of methyl tert-butyl ether, and the organic layers were combined. The combined organic layers were dried over anhydrous magnesium sulfate, filtered to give a filtrate, which was concentrated, and the crude product obtained was purified by column chromatography on silica gel (200-300 mesh) with ethyl acetate/petroleum ether as eluent to give the desired product.
TABLE 2 yields of 4- (phenylethynyl) anisole with different bases
| Numbering device | Alkali | Yield% |
| 1 | Potassium hydroxide | 31 |
| 2 | Sodium bicarbonate | 69 |
Comparative example 1
To a 250mL round bottom flask was added 0.76g (4 mmol) of cuprous iodide, 30mL of N, N-dimethylformamide in sequence, and the mixture was stirred at room temperature for half an hour. Then, 0.56g (4 mmol) of potassium carbonate was added in this order, 2.0g of the mercapto resin obtained in example 1 was heated to 85℃and reacted at a constant temperature for 16 hours. The reaction solution was cooled to room temperature, filtered, and the filter cake was rinsed with 10mL of N, N-dimethylformamide, and dried by suction to obtain a solid catalyst.
To a 100mL round-bottomed flask was added, in order, 1.9g (6 mmol) of the prepared copper-supported catalyst (0.3 mmol), 1.7g (12 mmol) of potassium carbonate, 1.4g (6 mmol) of p-methoxyiodobenzene, 50mL of water, and stirred at room temperature for 5 minutes. Then 0.68g (6.6 mmol) of phenylacetylene was added thereto, and the mixture was refluxed under nitrogen atmosphere for 18 hours. Cooled to room temperature, 50mL of methyl tert-butyl ether was added, filtered, the filtrate was poured into a separating funnel, and extracted once with 20mL of methyl tert-butyl ether, and the organic layers were combined. The combined organic layers were dried over anhydrous magnesium sulfate, filtered to give a filtrate which was concentrated, and the crude product obtained was purified by column chromatography on silica gel (200-300 mesh) with ethyl acetate/petroleum ether as eluent to give the desired product in 5% yield.
Claims (20)
1. The preparation method of the copper-supported catalyst is characterized by comprising the following steps of: in an organic solvent, under the action of alkali, a Cu (I) compound, sulfhydryl resin and phosphine ligand react to obtain the catalyst; wherein the mercapto resin is prepared by a process comprising the step of reacting chloromethyl polystyrene resin with thiourea.
2. The method for preparing a copper-supported catalyst according to claim 1,
the specification of the chloromethyl polystyrene resin is 100-500 meshes;
and/or the Cl content in the chloromethyl polystyrene resin is 0.1-3 mmol/g;
and/or the organic solvent is an amide solvent and/or a nitrile solvent;
and/or the Cu (I) compound is one or more of cuprous bromide, cuprous iodide and cuprous oxide;
and/or the molar concentration of the Cu (I) compound in the organic solvent is 0.01-1 mol/L;
and/or the phosphine ligand is one or more of 1, 10-phenanthroline, triphenylphosphine, 1' -bis-diphenylphosphino ferrocene and 1, 2-bis (diphenylphosphino) propane;
and/or the molar ratio of the phosphine ligand to the Cu (I) compound is 5:1-1:1;
and/or the alkali is one or more of hydroxide, carbonate, phosphate, MCN and R ' OM ', wherein M is alkali metal, R ' is C 1-4 Alkyl, M' is an alkali metal;
and/or the molar ratio of the base to the Cu (I) compound is 5:1-1:5;
and/or the mass concentration of the sulfhydryl resin in the organic solvent is 0.01-1 g/mL;
and/or the reaction time of the reaction is 2-30 hours;
and/or the reaction temperature of the reaction is 50-110 ℃.
3. The method for preparing a copper-supported catalyst according to claim 2,
the specification of the chloromethyl polystyrene resin is 100-200 meshes;
and/or the Cl content in the chloromethyl polystyrene resin is 0.8-1.2 mmol/g;
and/or the amide solvent is one or more of N, N-dimethylacetamide, N-dimethylformamide and N-methylpyrrolidone;
and/or the Cu (I) compound is cuprous iodide;
and/or the molar concentration of the Cu (I) compound in the organic solvent is 0.1-0.2 mol/L;
and/or, the phosphine ligand is triphenylphosphine;
and/or the molar ratio of the phosphine ligand to the Cu (I) compound is 4:1-1:1;
and/or, the alkali is carbonate;
and/or the molar ratio of the alkali to the Cu (I) compound is 2:1-1:2;
and/or the mass concentration of the sulfhydryl resin in the organic solvent is 0.05-0.08 g/mL;
and/or the reaction time of the reaction is 12-20 hours;
and/or the reaction temperature of the reaction is 70-90 ℃.
4. The method for preparing a copper-supported catalyst according to claim 2, wherein the amide solvent is N, N-dimethylformamide;
and/or the hydroxide is potassium hydroxide;
and/or the carbonate is one or more of potassium carbonate, sodium carbonate and cesium carbonate;
and/or, the phosphate is sodium phosphate;
and/or, M is sodium;
and/or R' is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or tert-butyl,
and/or M' is potassium or sodium.
5. The method for preparing a copper-supported catalyst according to claim 2, wherein the carbonate is potassium carbonate and/or sodium carbonate;
and/or, R' is tert-butyl.
6. The method for preparing a copper-supported catalyst according to claim 2, wherein the carbonate is potassium carbonate;
and/or R 'OM' is potassium tert-butoxide or sodium tert-butoxide.
7. A copper-supported catalyst prepared by the method for preparing a copper-supported catalyst according to any one of claims 1 to 6.
8. A method for preparing a compound of formula I, comprising the steps of: under the protection gas, in water, under the action of a surfactant, alkali and the copper-supported catalyst of claim 7, the compound shown in the formula II and the compound shown in the formula III are subjected to the coupling reaction shown in the following,
wherein R is 1 、R 2 、R 3 、R 4 And R is 5 Are each independently hydrogen, C 1-8 Alkyl, C 1-8 Alkoxy, nitro, -C (=o) R 3-1 Halogen, or halogen-substituted C 1-8 An alkyl group;
x' is chlorine, bromine or iodine;
R 6 is C 1-8 Alkyl or C 6-20 An aryl group;
R 3-1 is C 1-8 An alkyl group.
9. The process for preparing a compound of formula I as claimed in claim 8,
when R is 1 、R 2 、R 3 、R 4 And R is 5 Each independently is C 1-8 In the case of alkyl, said C 1-8 Alkyl is C 1-4 An alkyl group;
and/or when R 1 、R 2 、R 3 、R 4 And R is 5 Each independently is C 1-8 In the case of alkoxy, said C 1-8 Alkoxy is C 1-4 An alkoxy group;
and/or when R 1 、R 2 、R 3 、R 4 And R is 5 Each independently a halogen, wherein the halogen is fluorine, chlorine, bromine or iodine;
and/or when R 1 、R 2 、R 3 、R 4 And R is 5 Each independently halogen substituted C 1-8 When alkyl, theHalogen of (2) is fluorine, chlorine, bromine or iodine; the C is 1-8 Alkyl is C 1-4 An alkyl group;
and/or when R 1 、R 2 、R 3 、R 4 And R is 5 Each independently is-C (=O) R 3-1 When said R is 3-1 Is C 1-4 An alkyl group;
and/or, X' is iodine;
and/or when R 6 Is C 1-8 In the case of alkyl, said C 1-8 Alkyl is C 1-4 An alkyl group;
and/or when R 6 Is C 6-20 Aryl, the C 6-20 Aryl is C 6-14 Aryl groups.
10. The process for preparing a compound of formula I as claimed in claim 9,
when R is 1 、R 2 、R 3 、R 4 And R is 5 Each independently is C 1-8 In the case of alkyl, said C 1-8 Alkyl is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or tert-butyl;
and/or when R 1 、R 2 、R 3 、R 4 And R is 5 Each independently is C 1-8 In the case of alkoxy, said C 1-8 Alkoxy is methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy or tert-butoxy;
and/or when R 1 、R 2 、R 3 、R 4 And R is 5 Each independently a halogen, the halogen being chlorine;
and/or when R 1 、R 2 、R 3 、R 4 And R is 5 Each independently halogen substituted C 1-8 When alkyl, halogen is fluorine;
and/or, the C 1-8 Alkyl is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or tert-butyl;
and/or when R 1 、R 2 、R 3 、R 4 And R is 5 Each independently is-C (=O) R 3-1 When said R is 3-1 Methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or tert-butyl;
and/or when R 6 Is C 1-8 In the case of alkyl, said C 1-8 Alkyl is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or tert-butyl;
and/or when R 6 Is C 6-20 Aryl, the C 6-20 Aryl is phenyl, naphthyl or anthracenyl.
11. The process for preparing a compound of formula I as claimed in claim 9,
when R is 1 、R 2 、R 3 、R 4 And R is 5 Each independently is C 1-8 In the case of alkyl, said C 1-8 Alkyl is methyl;
and/or when R 1 、R 2 、R 3 、R 4 And R is 5 Each independently is C 1-8 In the case of alkoxy, said C 1-8 Alkoxy is methoxy;
and/or when R 1 、R 2 、R 3 、R 4 And R is 5 Each independently halogen substituted C 1-8 In the case of alkyl, said C 1-8 Alkyl is methyl;
and/or when R 1 、R 2 、R 3 、R 4 And R is 5 Each independently is-C (=O) R 3-1 When said R is 3-1 Is methyl;
and/or when R 6 Is C 6-20 Aryl, the C 6-20 Aryl is phenyl.
12. The process for preparing a compound of formula I as claimed in claim 8,
said R is 1 、R 2 、R 4 And R is 5 Is hydrogen, said R 3 Is C 1-8 Alkyl group、C 1-8 Alkoxy, nitro, -C (=o) R 3-1 Halogen, or halogen-substituted C 1-8 An alkyl group.
13. A process for the preparation of a compound of formula I as claimed in any one of claims 8 to 12,
said R is 3 C substituted by halogen 1-8 Alkyl, C 1-8 Alkyl or C 1-8 An alkoxy group;
and/or, the R 6 Is C 6-20 Aryl groups.
14. A process for the preparation of a compound of formula I as claimed in any one of claims 8 to 12,
the compound shown in the formula II is any one of the following compounds:
15. a process for the preparation of a compound of formula I as claimed in any one of claims 8 to 12,
the protective gas is nitrogen and/or argon;
and/or the molar concentration of the compound shown as the formula II in the water is 0.01-1 mol/L;
and/or the surfactant is one or more of tetrabutylammonium bromide, tetrabutylammonium chloride, polyethylene glycol and sodium dodecyl sulfate;
and/or the molar ratio of the surfactant to the compound shown as the formula II is 1:10-10:1;
and/or the alkali is carbonate and/or hydroxide;
and/or the molar ratio of the alkali to the compound shown as the formula II is 1:10-10:1;
and/or the molar ratio of copper in the copper-supported catalyst to the compound shown in the formula II is 1:200-1:5;
and/or the molar ratio of the compound shown in the formula III to the compound shown in the formula II is 1:1-3:1;
and/or the reaction time of the reaction is 10-30 hours;
and/or the reaction temperature of the reaction is 90-130 ℃.
16. The process for preparing a compound of formula I as claimed in claim 15,
the protective gas is nitrogen;
and/or the molar concentration of the compound shown as the formula II in the water is 0.1-0.2 mol/L;
and/or the surfactant is tetrabutylammonium bromide and/or polyethylene glycol;
and/or the molar ratio of the surfactant to the compound shown as the formula II is 1:2-2:1;
and/or, the alkali is carbonate;
and/or the molar ratio of the alkali to the compound shown as the formula II is 1:1-3:1;
and/or the molar ratio of copper in the copper-supported catalyst to the compound shown in the formula II is 1:100-1:10;
and/or the molar ratio of the compound shown in the formula III to the compound shown in the formula II is 1:1-2:1;
and/or the reaction time of the reaction is 16-20 hours;
and/or the reaction temperature of the reaction is 100-110 ℃.
17. The process for preparing a compound of formula I as claimed in claim 15,
the surfactant is tetrabutylammonium bromide;
and/or the carbonate is one or more of sodium carbonate, potassium carbonate and/or cesium carbonate;
and/or the hydroxide is sodium hydroxide and/or potassium hydroxide;
and/or the mol ratio of the compound shown in the formula III to the compound shown in the formula II is 1:1-1.5:1.
18. The method of claim 15, wherein the carbonate is potassium carbonate.
19. The process for preparing a compound of formula I according to any one of claims 8 to 12, wherein the reaction is completed with recovery of the copper-supported catalyst.
20. The method for preparing a compound as defined in claim 19, wherein the recovery of the copper-supported catalyst is to filter the reaction solution after the completion of the reaction to obtain the copper-supported catalyst.
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| US4215066A (en) * | 1977-11-10 | 1980-07-29 | Produits Chimiques Ugine Kuhlmann | Binuclear rhodium complex as a hydroformylation and hydrogenation catalyst |
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