CN113861098A - Synthetic method of indole derivative - Google Patents
Synthetic method of indole derivative Download PDFInfo
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- CN113861098A CN113861098A CN202111045501.8A CN202111045501A CN113861098A CN 113861098 A CN113861098 A CN 113861098A CN 202111045501 A CN202111045501 A CN 202111045501A CN 113861098 A CN113861098 A CN 113861098A
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- China
- Prior art keywords
- reaction
- catalyst
- naphthylamine
- indole
- synthesizing
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- 150000002475 indoles Chemical class 0.000 title claims abstract description 18
- 238000010189 synthetic method Methods 0.000 title claims description 3
- 238000006243 chemical reaction Methods 0.000 claims abstract description 100
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims abstract description 91
- 239000003054 catalyst Substances 0.000 claims abstract description 77
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N N-phenyl amine Natural products NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims abstract description 42
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims abstract description 23
- -1 aniline compound Chemical class 0.000 claims abstract description 21
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 claims abstract description 20
- 238000000034 method Methods 0.000 claims abstract description 18
- 229910052593 corundum Inorganic materials 0.000 claims abstract description 16
- 229910001845 yogo sapphire Inorganic materials 0.000 claims abstract description 16
- 230000002194 synthesizing effect Effects 0.000 claims abstract description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims abstract description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims abstract description 12
- 229940054051 antipsychotic indole derivative Drugs 0.000 claims abstract description 9
- 238000004440 column chromatography Methods 0.000 claims abstract description 7
- 239000003208 petroleum Substances 0.000 claims abstract description 7
- 238000000926 separation method Methods 0.000 claims abstract description 7
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims abstract description 6
- 238000003756 stirring Methods 0.000 claims abstract description 6
- 238000006555 catalytic reaction Methods 0.000 claims abstract description 5
- 230000002378 acidificating effect Effects 0.000 claims abstract description 4
- 239000003480 eluent Substances 0.000 claims abstract description 4
- 239000012074 organic phase Substances 0.000 claims abstract description 4
- 238000002390 rotary evaporation Methods 0.000 claims abstract description 4
- 239000002904 solvent Substances 0.000 claims abstract description 4
- 238000005470 impregnation Methods 0.000 claims abstract description 3
- JBIJLHTVPXGSAM-UHFFFAOYSA-N 2-naphthylamine Chemical compound C1=CC=CC2=CC(N)=CC=C21 JBIJLHTVPXGSAM-UHFFFAOYSA-N 0.000 claims description 25
- RUFPHBVGCFYCNW-UHFFFAOYSA-N 1-naphthylamine Chemical compound C1=CC=C2C(N)=CC=CC2=C1 RUFPHBVGCFYCNW-UHFFFAOYSA-N 0.000 claims description 12
- 239000000203 mixture Substances 0.000 claims description 10
- 239000007787 solid Substances 0.000 claims description 9
- 238000001816 cooling Methods 0.000 claims description 8
- 239000000047 product Substances 0.000 claims description 8
- 239000002253 acid Substances 0.000 claims description 6
- 239000012295 chemical reaction liquid Substances 0.000 claims description 6
- 238000011068 loading method Methods 0.000 claims description 4
- 238000002156 mixing Methods 0.000 claims description 4
- 238000004064 recycling Methods 0.000 claims description 4
- 238000005303 weighing Methods 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 239000007864 aqueous solution Substances 0.000 claims description 3
- 238000001035 drying Methods 0.000 claims description 3
- 239000012065 filter cake Substances 0.000 claims description 3
- 238000001914 filtration Methods 0.000 claims description 3
- 238000000227 grinding Methods 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 238000002791 soaking Methods 0.000 claims description 3
- 239000011949 solid catalyst Substances 0.000 claims description 3
- FTZQXOJYPFINKJ-UHFFFAOYSA-N 2-fluoroaniline Chemical compound NC1=CC=CC=C1F FTZQXOJYPFINKJ-UHFFFAOYSA-N 0.000 claims description 2
- DPJCXCZTLWNFOH-UHFFFAOYSA-N 2-nitroaniline Chemical compound NC1=CC=CC=C1[N+]([O-])=O DPJCXCZTLWNFOH-UHFFFAOYSA-N 0.000 claims description 2
- AEIOZWYBDBVCGW-UHFFFAOYSA-N 2-tert-butylaniline Chemical compound CC(C)(C)C1=CC=CC=C1N AEIOZWYBDBVCGW-UHFFFAOYSA-N 0.000 claims description 2
- NJXPYZHXZZCTNI-UHFFFAOYSA-N 3-aminobenzonitrile Chemical compound NC1=CC=CC(C#N)=C1 NJXPYZHXZZCTNI-UHFFFAOYSA-N 0.000 claims description 2
- XJCVRTZCHMZPBD-UHFFFAOYSA-N 3-nitroaniline Chemical compound NC1=CC=CC([N+]([O-])=O)=C1 XJCVRTZCHMZPBD-UHFFFAOYSA-N 0.000 claims description 2
- YBAZINRZQSAIAY-UHFFFAOYSA-N 4-aminobenzonitrile Chemical compound NC1=CC=C(C#N)C=C1 YBAZINRZQSAIAY-UHFFFAOYSA-N 0.000 claims description 2
- KRZCOLNOCZKSDF-UHFFFAOYSA-N 4-fluoroaniline Chemical compound NC1=CC=C(F)C=C1 KRZCOLNOCZKSDF-UHFFFAOYSA-N 0.000 claims description 2
- TYMLOMAKGOJONV-UHFFFAOYSA-N 4-nitroaniline Chemical compound NC1=CC=C([N+]([O-])=O)C=C1 TYMLOMAKGOJONV-UHFFFAOYSA-N 0.000 claims description 2
- NCBZRJODKRCREW-UHFFFAOYSA-N m-anisidine Chemical compound COC1=CC=CC(N)=C1 NCBZRJODKRCREW-UHFFFAOYSA-N 0.000 claims description 2
- VZDNXXPBYLGWOS-UHFFFAOYSA-N methyl 3-aminobenzoate Chemical compound COC(=O)C1=CC=CC(N)=C1 VZDNXXPBYLGWOS-UHFFFAOYSA-N 0.000 claims description 2
- LZXXNPOYQCLXRS-UHFFFAOYSA-N methyl 4-aminobenzoate Chemical compound COC(=O)C1=CC=C(N)C=C1 LZXXNPOYQCLXRS-UHFFFAOYSA-N 0.000 claims description 2
- VAMXMNNIEUEQDV-UHFFFAOYSA-N methyl anthranilate Chemical compound COC(=O)C1=CC=CC=C1N VAMXMNNIEUEQDV-UHFFFAOYSA-N 0.000 claims description 2
- KQSABULTKYLFEV-UHFFFAOYSA-N naphthalene-1,5-diamine Chemical compound C1=CC=C2C(N)=CC=CC2=C1N KQSABULTKYLFEV-UHFFFAOYSA-N 0.000 claims description 2
- VMPITZXILSNTON-UHFFFAOYSA-N o-anisidine Chemical compound COC1=CC=CC=C1N VMPITZXILSNTON-UHFFFAOYSA-N 0.000 claims description 2
- RNVCVTLRINQCPJ-UHFFFAOYSA-N o-toluidine Chemical compound CC1=CC=CC=C1N RNVCVTLRINQCPJ-UHFFFAOYSA-N 0.000 claims description 2
- BHAAPTBBJKJZER-UHFFFAOYSA-N p-anisidine Chemical compound COC1=CC=C(N)C=C1 BHAAPTBBJKJZER-UHFFFAOYSA-N 0.000 claims description 2
- 239000000463 material Substances 0.000 claims 1
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 abstract description 32
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 abstract description 17
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 abstract description 15
- 230000003197 catalytic effect Effects 0.000 abstract description 14
- 239000000758 substrate Substances 0.000 abstract description 8
- 150000001448 anilines Chemical class 0.000 abstract description 7
- 239000002994 raw material Substances 0.000 abstract description 5
- 230000015572 biosynthetic process Effects 0.000 abstract description 4
- 238000003786 synthesis reaction Methods 0.000 abstract description 4
- 238000001308 synthesis method Methods 0.000 abstract description 3
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Substances [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 89
- 239000002245 particle Substances 0.000 description 54
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 36
- 229910052697 platinum Inorganic materials 0.000 description 29
- 239000006227 byproduct Substances 0.000 description 14
- MRUOEOGYSDTCDK-UHFFFAOYSA-N 1h-cyclopenta[c]quinoline Chemical compound C1=CC=CC2=C3CC=CC3=CN=C21 MRUOEOGYSDTCDK-UHFFFAOYSA-N 0.000 description 10
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 9
- 238000005160 1H NMR spectroscopy Methods 0.000 description 9
- 230000035484 reaction time Effects 0.000 description 9
- 238000001228 spectrum Methods 0.000 description 9
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 8
- 238000004458 analytical method Methods 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 238000003917 TEM image Methods 0.000 description 6
- 230000009471 action Effects 0.000 description 6
- 238000001819 mass spectrum Methods 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 238000009826 distribution Methods 0.000 description 5
- 235000019439 ethyl acetate Nutrition 0.000 description 5
- 239000000543 intermediate Substances 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- FOZQOPBBZKHGGM-UHFFFAOYSA-N 9H-cyclopenta[f]isoquinoline Chemical compound C1=CN=CC=2C=CC=3C=CCC3C21 FOZQOPBBZKHGGM-UHFFFAOYSA-N 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- 125000003277 amino group Chemical group 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 238000009833 condensation Methods 0.000 description 4
- 230000005494 condensation Effects 0.000 description 4
- 230000008021 deposition Effects 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 125000000168 pyrrolyl group Chemical group 0.000 description 4
- 238000011084 recovery Methods 0.000 description 4
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 239000007806 chemical reaction intermediate Substances 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 3
- 229910000510 noble metal Inorganic materials 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- LUNOXNMCFPFPMO-UHFFFAOYSA-N 4-methoxy-1h-indole Chemical compound COC1=CC=CC2=C1C=CN2 LUNOXNMCFPFPMO-UHFFFAOYSA-N 0.000 description 2
- QJRWYBIKLXNYLF-UHFFFAOYSA-N 6-methoxy-1h-indole Chemical compound COC1=CC=C2C=CNC2=C1 QJRWYBIKLXNYLF-UHFFFAOYSA-N 0.000 description 2
- FSOPPXYMWZOKRM-UHFFFAOYSA-N 7-methoxy-1h-indole Chemical compound COC1=CC=CC2=C1NC=C2 FSOPPXYMWZOKRM-UHFFFAOYSA-N 0.000 description 2
- KGWPHCDTOLQQEP-UHFFFAOYSA-N 7-methylindole Chemical compound CC1=CC=CC2=C1NC=C2 KGWPHCDTOLQQEP-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- IKHGUXGNUITLKF-XPULMUKRSA-N acetaldehyde Chemical compound [14CH]([14CH3])=O IKHGUXGNUITLKF-XPULMUKRSA-N 0.000 description 2
- WPWMFJQLFZIYPV-UHFFFAOYSA-N aniline ethane-1,2-diol Chemical compound NC1=CC=CC=C1.C(CO)O WPWMFJQLFZIYPV-UHFFFAOYSA-N 0.000 description 2
- 239000012159 carrier gas Substances 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 230000009849 deactivation Effects 0.000 description 2
- 230000018044 dehydration Effects 0.000 description 2
- 238000006297 dehydration reaction Methods 0.000 description 2
- 238000006356 dehydrogenation reaction Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 125000006575 electron-withdrawing group Chemical group 0.000 description 2
- 150000002081 enamines Chemical class 0.000 description 2
- 150000002466 imines Chemical class 0.000 description 2
- 238000009776 industrial production Methods 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- DRYBMFJLYYEOBZ-UHFFFAOYSA-N methyl 1h-indole-5-carboxylate Chemical compound COC(=O)C1=CC=C2NC=CC2=C1 DRYBMFJLYYEOBZ-UHFFFAOYSA-N 0.000 description 2
- AYYOZKHMSABVRP-UHFFFAOYSA-N methyl 1h-indole-6-carboxylate Chemical compound COC(=O)C1=CC=C2C=CNC2=C1 AYYOZKHMSABVRP-UHFFFAOYSA-N 0.000 description 2
- AHEJURHRYJPYST-UHFFFAOYSA-N n-ethylnaphthalen-2-amine Chemical compound C1=CC=CC2=CC(NCC)=CC=C21 AHEJURHRYJPYST-UHFFFAOYSA-N 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 231100000572 poisoning Toxicity 0.000 description 2
- 230000000607 poisoning effect Effects 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000007363 ring formation reaction Methods 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- 238000005245 sintering Methods 0.000 description 2
- ZFRKQXVRDFCRJG-UHFFFAOYSA-N skatole Chemical compound C1=CC=C2C(C)=CNC2=C1 ZFRKQXVRDFCRJG-UHFFFAOYSA-N 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- IMROMDMJAWUWLK-UHFFFAOYSA-N Ethenol Chemical compound OC=C IMROMDMJAWUWLK-UHFFFAOYSA-N 0.000 description 1
- 235000000177 Indigofera tinctoria Nutrition 0.000 description 1
- 239000011149 active material Substances 0.000 description 1
- 238000005054 agglomeration Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000007036 catalytic synthesis reaction Methods 0.000 description 1
- 239000011280 coal tar Substances 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 229940097275 indigo Drugs 0.000 description 1
- COHYTHOBJLSHDF-UHFFFAOYSA-N indigo powder Natural products N1C2=CC=CC=C2C(=O)C1=C1C(=O)C2=CC=CC=C2N1 COHYTHOBJLSHDF-UHFFFAOYSA-N 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 238000013173 literature analysis Methods 0.000 description 1
- VKWJMTLAAJULGF-UHFFFAOYSA-N methoxymethyl formate Chemical group COCOC=O VKWJMTLAAJULGF-UHFFFAOYSA-N 0.000 description 1
- TZIHFWKZFHZASV-UHFFFAOYSA-N methyl formate Chemical group COC=O TZIHFWKZFHZASV-UHFFFAOYSA-N 0.000 description 1
- 238000001000 micrograph Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- JVJQPDTXIALXOG-UHFFFAOYSA-N nitryl fluoride Chemical group [O-][N+](F)=O JVJQPDTXIALXOG-UHFFFAOYSA-N 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 108091008695 photoreceptors Proteins 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000007420 reactivation Effects 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000011946 reduction process Methods 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 235000013599 spices Nutrition 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- 239000010409 thin film Substances 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/56—Ring systems containing three or more rings
- C07D209/58—[b]- or [c]-condensed
- C07D209/60—Naphtho [b] pyrroles; Hydrogenated naphtho [b] pyrroles
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J23/00—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00
- B01J23/38—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of noble metals
- B01J23/40—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of noble metals of the platinum group metals
- B01J23/42—Platinum
-
- B01J35/23—
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/584—Recycling of catalysts
Abstract
The invention belongs to the technical field of indole synthesis, and provides a synthesis method of indole derivatives in order to solve the problems that the reaction for synthesizing indole and derivatives thereof by using ethylene glycol as a raw material is relatively harsh, the structure of a main catalyst is complex, the price is high and the like. With acidic Al2O3The Pt/Al loaded Pt is prepared by an impregnation method as a carrier2O3Catalyst, adopting aniline compound, glycol and prepared Pt/Al2O3And (2) carrying out catalytic reaction on a catalyst, controlling the reaction temperature to be 190 ℃, reacting for 24h, adding water and stirring uniformly after the reaction is finished, then extracting with dichloromethane, carrying out rotary evaporation and concentration on an organic phase to remove a solvent, and then carrying out column chromatography separation by using petroleum ether and ethyl acetate as eluents to obtain a target product. Has better catalytic effect in reaction of ethylene glycol phenylaminePt/Al of2O3The catalytic system of the supported catalyst is researched in a broad spectrum, and the substrate range of substituted aniline is mainly expanded.
Description
Technical Field
The invention belongs to the technical field of indole synthesis, and particularly relates to a synthesis method of an indole derivative.
Background
Indole, also called benzopyrrole, is composed of a benzene ring and a pyrrole ring. Indoles and their derivatives are present in a wide variety of organisms, and were originally discovered by degradation of indigo. Coal tar, perfume, amino acid and hormone all contain indole and indole derivatives, and the odor of excrement is greatly related to 3-methylindole contained in the excrement. In addition, indole and derivatives thereof are widely applied in the field of medicine as very important intermediates or characteristic structures.
The catalytic systems in the existing methods for synthesizing indole and derivatives thereof are all multi-component catalysis, and the main catalysts are all noble metals, and have complex structures and high price. The one-step catalytic synthesis of indole and its derivatives from aniline and ethylene glycol system is of great interest because of its cheap reaction raw materials, few reaction steps, harmless by-products and easy separation (by-products are water and hydrogen). The reaction for synthesizing indole from aniline and ethylene glycol has many advantages, such as few reaction steps, easily available raw materials, only water and hydrogen as byproducts, no environmental pollution and the like, so that the method is widely researched and applied to industrial production of indole.
In view of the fact that the yield of the domestic coal-to-ethylene glycol is greatly increased year by year and the quality index does not meet the requirement of producing polyester, the development and research of high-value fine conversion of the ethylene glycol have important market requirements and economic significance. Indole and derivatives thereof are used as one of ethylene glycol downstream products, and are widely applied in the fields of biology, medicines, foods, dyes, spices, pesticides and the like, and the synthesis research of indole and derivatives thereof provides an effective way for high-value conversion of ethylene glycol.
Disclosure of Invention
The invention provides a synthesis method of indole derivatives, aiming at solving the problems that the reaction for synthesizing indole and derivatives thereof by using ethylene glycol as a raw material at present is relatively harsh in conditions, complex in structure of a main catalyst, high in price and the like.
The invention is realized by the following technical scheme: a process for synthesizing indole derivative from acidic Al2O3The Pt/Al loaded Pt is prepared by an impregnation method as a carrier2O3Catalyst, adopting aniline compound, glycol and prepared Pt/Al2O3And (2) carrying out catalytic reaction on a catalyst, controlling the reaction temperature to be 190 ℃, reacting for 24h, adding water and stirring uniformly after the reaction is finished, then extracting with dichloromethane, carrying out rotary evaporation and concentration on an organic phase to remove a solvent, and then carrying out column chromatography separation by using petroleum ether and ethyl acetate as eluents to obtain a target product.
The Pt/Al2O3The preparation method of the catalyst comprises the following steps: firstly, carrying acid carrier Al2O3Placing the mixture in a muffle furnace, roasting the mixture for 4 hours at 500 ℃, and naturally cooling the mixture to room temperature; weighing 1 g of carrier, and soaking in 30 mL of chloroplatinic acid H with the mass concentration of 3%2PtCl6·6H2Stirring the mixture in an O aqueous solution for 24 hours at normal temperature, fully and uniformly mixing reaction liquid, filtering, drying a solid filter cake for 12 hours at 120 ℃, grinding the solid, roasting the ground solid in a muffle furnace for 4 hours at 500 ℃, and naturally cooling to obtain the Pt/Al with the Pt loading of 3wt%2O3A catalyst; the catalyst is activated after being recycled for 4 times: the solid catalyst is washed by water, filtered, roasted for 5 hours at 500 ℃, and cooled for recycling.
The aniline compound is as follows: alkyl-, methoxy-, carbomethoxy-, nitro-or fluorine-substituted anilines, and 1-naphthylamine or 2-naphthylamine.
The aniline compound is as follows:Nany one of-methylaniline, o-methoxyaniline, m-methoxyaniline, p-methoxyaniline, o-carbomethoxyaniline, m-carbomethoxyaniline, p-carbomethoxyaniline, o-methylaniline, o-tert-butylaniline, o-fluoroaniline, p-fluoroaniline, o-nitroaniline, m-nitroaniline, p-nitroaniline, m-cyanoaniline, p-cyanoaniline, 1-naphthylamine, 2-naphthylamine or 1, 5-diaminonaphthalene.
The aniline compound is as follows: aniline or 2-naphthylamine substituted with an electron donating group.
The aniline compound is 2-naphthylamine.
1mmol of aniline compound, 54mmol of ethylene glycol and 0.015mmol of catalyst; the column chromatography is eluted according to the volume ratio of petroleum ether to ethyl acetate of 90: 10.
The invention has better catalytic effect on Pt/Al in the reaction of ethylene glycol phenylamine2O3The catalytic system of the supported catalyst is researched in a broad spectrum, and the substrate range of substituted aniline is mainly expanded. The result shows that when the electron-donating group exists on the aniline, the reaction yield is higher; when the substituent on aniline is strong electron-withdrawing group or the ortho position of amino group has large group, the reaction yield is low. In testing some naphthylamine substrates, the reaction yield of 2-naphthylamine was found to be the highest, reaching 95%. Gas phase mass spectrum is used together with detection and analysis in the reaction process of 2-naphthylamine and ethylene glycol for synthesizing indole in one step, several possible reaction intermediates and byproducts are presumed, and a possible reaction mechanism is presumed: firstly, glycol is dehydrated under the action of alumina and is converted into acetaldehyde, the acetaldehyde and amino are subjected to aldehyde-amine condensation to remove water, and finally, under the action of metal platinum, dehydrogenation cyclization is carried out to form pyrrole ring, thus completing the reaction process.
In order to increase the utilization efficiency of the noble metal platinum in the catalyst, the catalyst is recycled in several steps. The result shows that in the first 4 times of reactions, the catalytic effect of the catalyst is weakened slightly, when the reaction times reach 5 times, the yield of the reaction is reduced greatly, which indicates that the catalyst has relatively good stability, can be recycled for 4 times, and the accumulated participation reaction time is 96 hours, but the catalytic effect is not greatly reduced, so that the catalyst cost can be greatly reduced, further the economic benefit of the invention is more prominent, and the core competitiveness of the technology of the invention and the possibility of industrial production are greatly increased. The microscopic morphology characterization of the original catalyst and the recovered catalyst which respectively undergoes 1, 3 and 5 times of reaction is carried out by an electron microscope, and the result shows that the distribution of platinum particles on the carrier in the original catalyst is relatively uniform, and the distribution and the particle size become disordered along with the increase of the reaction times. It follows from this that: the loss of platinum particles during the reaction process occurs, and the platinum particles are fused and combined into larger particles under the high temperature condition, so that the effective contact area of the catalyst is reduced, which is the main reason for reducing the catalytic efficiency.
Drawings
FIG. 1 is a reaction equation for synthesizing indole derivatives from aniline derivatives;
FIG. 2 isN-ethyl-2-naphthylamine mass and structural formula;
FIG. 3 is a mass spectrum and a structural formula of a byproduct generated by the reaction of 2-naphthylamine and ethylene glycol;
FIG. 4 shows the trend of reaction intermediates and by-products of 2-naphthylamine with ethylene glycol;
FIG. 5 is a diagram showing a process of presuming the reaction of 2-naphthylamine with ethylene glycol;
FIG. 6 is a reaction equation for the reaction of 2-naphthylamine with ethylene glycol to produce 4, 5-benzindole;
FIG. 7 shows the mass and yield of the catalyst after four cycles;
FIG. 8 shows Pt/Al of a newly prepared supported catalyst2O3TEM image of (Pt particle average particle diameter: 5.0 nm);
FIG. 9 shows Pt/Al after primary reaction2O3TEM image of (Pt particle average particle diameter: 5.4 nm);
FIG. 10 shows Pt/Al after three reactions2O3TEM image of (Pt particle average particle diameter: 5.3 nm);
FIG. 11 shows Pt/Al after five reactions2O3TEM image of (Pt particle average particle diameter: 6.1 nm);
FIG. 12 is a graph showing the relationship between the particle size and the particle size variance of platinum in the catalyst and the number of reactions;
FIG. 13 is a nuclear magnetic spectrum of 7-methylindole;
FIG. 14 is a nuclear magnetic spectrum of 7-methoxyindole;
FIG. 15 is a nuclear magnetic spectrum of 4-methoxyindole;
FIG. 16 is a nuclear magnetic spectrum of 6-methoxyindole;
FIG. 17 is a nuclear magnetic spectrum of 6-carbomethoxyindole;
FIG. 18 is a nuclear magnetic spectrum of 5-carbomethoxyindole;
FIG. 19 is a nuclear magnetic spectrum of 4, 5-benzindole;
FIG. 20 is a nuclear magnetic spectrum of 6-amino-6, 7-benzindole;
FIG. 21 is a nuclear magnetic spectrum of N-methyl-6, 7-benzindole.
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below, and it is obvious that the described embodiments are some embodiments of the present invention, but not all embodiments; all other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Firstly, experimental reagents and instruments: the experimental apparatus is shown in Table 1, and the reagents are shown in Table 2.
Table 1: laboratory apparatus
Table 2: experimental reagent
Synthesis of di-and indole derivatives
1. The experimental method comprises the following steps:
preparation of the supported catalyst: firstly, carrying acid carrier Al2O3Placing in a muffle furnace, roasting at 500 ℃ for 4h, and naturally cooling to room temperature. Weighing 1 g of carrier, and soaking in 30 mL of chloroplatinic acid H with the mass concentration of 3%2PtCl6·6H2Stirring the mixture in an O aqueous solution for 24 hours at normal temperature, fully and uniformly mixing reaction liquid, filtering, drying a solid filter cake for 12 hours at 120 ℃, grinding the solid, roasting the ground solid in a muffle furnace for 4 hours at 500 ℃, and naturally cooling to obtain the Pt/Al with the Pt loading of 3wt%2O3A catalyst. Reaction conditions are as follows: the dosage of the aniline compound is 1mmol, the dosage of the ethylene glycol is 54mmol, the dosage of the catalyst is 0.015mmol, the reaction time is 24h, and the reaction temperature is 190 ℃.
Separation conditions are as follows: after the reaction is finished, water is added and the mixture is stirred uniformly, then dichloromethane is used for extraction, organic phase is subjected to rotary evaporation and concentration to remove solvent, petroleum ether and ethyl acetate are used as eluent, and the target product is obtained through column chromatography separation. The general equation of the reaction is shown in FIG. 1.
2. The experimental results are as follows:
alkyl, methoxy, methyl formate, nitro, fluorine substituted aniline and naphthylamine are selected for substrate expansibility study, and the reaction conditions are as follows: 0.015mmol of catalyst, 3ml of glycol and 1mmol of aniline react at 190 ℃ for 24h, and the catalyst loading is 3 wt%. The structure and yield of the obtained indole derivative are shown in table 3.
Table 3: results of synthetic experiments on indole derivatives
The results of nuclear magnetic analysis of the obtained product were as follows:
1. 7-methylindole
：1H NMR (400 MHz, CDCl3) δ 7.96 (s, 1H), 7.50 (d, J = 7.7 Hz, 1H), 7.14 (t, J = 4.0 Hz, 1H), 7.07 – 6.97 (m, 2H), 6.55 (dd, J = 3.1, 2.1 Hz, 1H), 2.46 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 135.3, 127.3, 123.8, 122.4, 120.2, 120.0, 118.4, 103.0, 16.6。
2. 7-methoxyindole
：1H NMR (400 MHz, CDCl3) δ 8.28 (s, 1H), 7.16 (d, J = 7.9 Hz, 1H), 7.06 (t, J = 2.7 Hz, 1H), 6.94 (td, J = 7.9, 1.2 Hz, 1H), 6.54 (d, J = 7.7 Hz, 1H), 6.43 (dd, J = 3.2, 1.8 Hz, 1H), 3.86 (s, 3H).13C NMR (100 MHz, CDCl3) δ 146.1, 129.1, 126.4, 123.6, 120.1, 113.4, 102.8, 101.7, 55.3。
3. 4-methoxyindole
：1H NMR (400 MHz, CDCl3) δ 7.88 (s, 1H), 7.45 – 7.35 (m, 1H), 6.93 (s, 1H), 6.70 (s, 2H), 6.36 (s, 1H), 3.71 (d, J = 1.7 Hz, 3H).13C NMR (100MHz, CDCl3) δ 156.3, 136.5, 123.0, 122.1, 121.2, 109.8, 102.3, 94.5, 55.6。
4. 6-methoxyindole
：1H NMR (400 MHz, CDCl3) δ 8.08 (s, 1H), 7.07 (t, J = 7.6 Hz, 1H), 7.03 (t, J = 2.8 Hz, 1H), 6.94 (d, J = 8.2, Hz, 1H), 6.59 (ddd, J = 3.2, 2.2, 0.9 Hz, 1H), 6.46 (d, J = 8.0, Hz , 1H), 3.89 (s, 3H).13C NMR (100 MHz, CDCl3) δ 153.3, 137.2, 122.7, 122.6, 118.5, 104.4, 99.8, 99.49, 55.3。
5. Indole-6-carboxylic acid methyl ester
：1H NMR (400 MHz, CDCl3) δ 8.47 – 8.41 (m, 1H), 8.39 (s, 1H), 7.91 (dd, J = 8.6, 1.6 Hz, 1H), 7.44 – 7.37 (m, 1H), 7.28 (dd, J = 3.3, 2.4 Hz, 1H), 6.65 (ddd, J = 3.2, 2.0, 0.9 Hz, 1H), 3.93 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 168.2, 138.3, 127.4, 125.4, 123.8, 123.4, 122.0, 110.7, 104.1, 51.9。
6. Indole-5-carboxylic acid methyl ester
：1H NMR (400 MHz, CDCl3) δ 8.47 (s, 1H), 8.17 (s, 1H), 7.82 (dd, J = 8.3, 1.5 Hz, 1H), 7.66 (d, J = 8.3 Hz, 1H), 7.38 (t, J = 2.8 Hz, 1H), 6.61 (ddd, J = 3.2, 2.0, 1.0 Hz, 1H), 3.94 (s, 3H).13C NMR (100 MHz, CDCl3) δ 168.17, 135.1, 131.5, 127.5, 123.7, 120.9, 120.3, 113.4, 103.0, 52.0。
7. 4, 5-Benzoindoles
：1H NMR (400 MHz, CDCl3) δ 8.51 (s, 1H), 8.25 (dd, J = 8.2, 1.1 Hz, 1H), 7.90 (dt, J = 8.2, 0.9 Hz, 1H), 7.63 – 7.52 (m, 3H), 7.42 (m, 1H), 7.29 (t, J = 2.8 Hz, 1H), 7.10 (ddd, J = 3.1, 2.1, 0.9 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ 128.5, 125.7, 123.3, 123.0, 122.1, 112.7, 101.9, 31.9, 29.7, 29.4, 22.7, 14.1。
8. 6-amino-6, 7-benzindole
：1H NMR (400 MHz, CDCl3) δ 8.86 (s, 1H), 7.71 (d, J = 8.8 Hz, 1H), 7.48 (dd, J = 15.3, 8.5 Hz, 1H), 7.39 – 7.31 (m, 1H), 7.29 – 7.25 (m, 2H), 6.82 – 6.74 (m, 1H), 6.72 – 6.66 (m, 1H), 4.19 (s, 2H).13C NMR (100 MHz, CDCl3) δ 143.2, 126.1, 125.3, 122.4, 119.6, 113.3, 111.6, 110.2, 109.9, 108.7, 104.1, 29.7。
9、N-methyl-6, 7-benzindole
：1H NMR (400 MHz, CDCl3) δ 8.50 (d, J = 8.4 Hz, 1H), 7.98 (d, J = 8.0 Hz, 1H), 7.74 (d, J = 8.5 Hz, 1H), 7.60 – 7.51 (m, 2H), 7.43-7.50 (m, 1H), 7.08 (d, J = 3.0 Hz, 1H), 6.64 (d, J = 2.9 Hz, 1H), 4.30 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 131.4, 130.0, 129.2, 129.1, 125.9, 125.2, 123.5, 123.3, 121.1, 121.0, 120.6, 102.1, 38.5。
The results show that the reaction system has good substrate universality, and a plurality of aniline derivatives can react with ethylene glycol to generate corresponding indole derivatives under the catalytic system. However, the yield of the reaction is relatively different, and the aniline derivative having a methyl formate group at the ortho-position of the amino group may not be smoothly reacted or the reaction yield may be poor due to steric hindrance. When strong electron-withdrawing group nitro and cyano are substituted on aniline, the reaction hardly occurs, but the aniline substituted by electron-donating group has higher reaction yield, the reaction yield of 2-naphthylamine can reach 95%, and the conversion rate is close to 100%. This phenomenon is presumed to be due to the fact that in the dehydration process of the amino hydrogen of aniline and the hydroxyl group of ethylene glycol, the process proceeds faster when the electron cloud density on the benzene ring is higher. Compared with 2-naphthylamine, the 2-naphthylamine has smaller steric hindrance and the 1-position has higher reactivity, so the reaction yield is higher.
The reaction yield of the 2-naphthylamine and the ethylene glycol is excellent, and the generated 4, 5-benzindole compound has various photo-thermal characteristics and can be applied to the fields of organic electroluminescent devices, organic solar cells, perovskite cells, organic thin film transistors or organic photoreceptors. The reaction route offers the possibility of subsequent chemical transformation of 4, 5-benzindole molecules with photothermal application.
3. Speculation on the reaction mechanism:
the 2-naphthylamine with the highest reaction yield is selected as a research object: the reaction liquid of the 2-naphthylamine and the ethylene glycol is analyzed by adopting gas chromatography-mass spectrometry (GC-MS), and the structures of a plurality of possible intermediates and byproducts are analyzed by combining original data obtained by literature analysis. The mass spectral peak area ratios of the intermediates as a function of time are shown in table 4.
Reaction and sampling methods: the using amount of the 2-naphthylamine is 1mmol, the using amount of the ethylene glycol is 54mmol, the using amount of the catalyst is 0.015mmol, the reaction temperature is 190 ℃, the reaction is cooled to room temperature after a certain time (1 h, 2 h, 3 h, 4h, 8 h, 12 h, 16 h, 20 h and 24 h), 0.2 mL of sample is respectively taken from the supernatant for standby detection, and the heating reaction is continued after sampling.
The reaction system was followed by analysis using a Japan Shimadzu GC MS-QP 2010 ultra gas chromatography-mass spectrometer (GC-MS) equipped with an AOS-5000 plus autosampler under the following analysis conditions: the method comprises the following steps of preparing a RestekRxi-5MS chromatographic column (30 m multiplied by 0.25 mm multiplied by 0.25 mu m), raising the initial temperature to 250 ℃ at the rate of 6 ℃/min (after 10 min is carried out, the injection temperature is 300 ℃, the linear velocity of a carrier gas is 36.9 cm/s, the pressure in front of the column is 55.5 kPa, the split ratio is 70:1, the carrier gas is high-purity nitrogen, the flow rate is 1.00 mL/min, an MS ion source is an EI source, the temperature is 230 ℃, the interface temperature of a mass spectrum and a chromatogram is 280 ℃, and the mass scanning range (m/z) is 29-250 amu.
Table 4: GC-MS analysis result of 4, 5-benzindole generated by reaction of 2-naphthylamine and ethylene glycol
According to the mass spectrum result and contrast with the standard spectrogram, presumeNThe-ethyl-2-naphthylamine may be a key intermediate of the reaction, and the mass spectrum and the structural formula are shown in figure 2; the structure of a by-product that may be produced is shown in fig. 3.
The trend of the peak areas of the intermediates, the byproducts and the products along with the time is shown in fig. 4, and it can be seen that the reaction product 4, 5-benzindole shows a continuous reduction trend after 4 hours, which indicates that the reaction time of the reaction still needs to be optimized, the reaction reaches the peak before 4 hours, the byproducts of the reaction gradually increase after 4 hours, the byproducts all take place by using the reaction product 4, 5-benzindole as a raw material, and a plurality of byproducts mostly take place substitution reaction with N-H on the pyrrole ring.
It is presumed that the amino group is more likely to undergo dehydration condensation with ethylene glycol at the initial stage of the reaction: ethylene glycol eliminates one molecule of water per se under the induction of acidic alumina, is converted into vinyl alcohol, is converted into acetaldehyde through proton transfer, removes one molecule of water from acetaldehyde and amino on naphthalene, completes aldehyde-amine condensation, the condensed imine is easily converted into enamine, then reacts with C-H at the No. 1 position of naphthalene under the action of platinum, removes one molecule of hydrogen, and finally generates the product 4, 5-benzindole.
The reaction mechanism is presumed to be shown in FIG. 5. According to the possible reaction sequence, the compound in FIG. 2NEthyl-2-naphthylamine is also a by-product, formed by reduction of imine or enamine to ethyl by the action of platinum adsorbed with H; in FIG. 3, the compound (3) and the compound (4) are 4, 5-benzindole products, which are obtained by similar conversion processes with naphthylamine.
4. Catalyst Pt/Al2O3Activation and reuse of
Pt/Al2O3The price of platinum as a carrier of the catalyst is high, and the reactivation and recycling effects of the supported catalyst after the catalyst participates in the reaction are researched.
The reduced activity of supported catalysts can be attributed to a number of reasons, such as catalyst poisoning and deactivation by coordinating species in the reaction mixture; or the crystal grain of the catalyst becomes bigger after the high-temperature reaction, the specific surface area is reduced, and the activity is reduced; or carbon deposition occurs on the surface of the active material after the reaction, so that the active component can not fully contact with reactants, and other reasons comprise loss and breakage. In this reaction, the catalyst is subjected to higher temperatures and conditions such as carbon deposition, sintering, run-off, etc. may occur. The catalyst recovered after the reaction is re-roasted at high temperature, so that the deactivation of the catalyst caused by factors such as poisoning, carbon deposition and the like can be basically eliminated.
A. The experimental method comprises the following steps: Pt/Al based on the highest yields of 2-naphthylamine and ethylene glycol in substrate development2O3The reaction for synthesizing 4, 5-benzindole under the catalysis of the catalyst is used for researching the activity reduction process of the catalyst. The reaction equation is shown in FIG. 6.
After the reaction is finished, standing the reaction liquid, cooling to room temperature, centrifuging the reaction liquid, taking supernatant, and mixing with Petroleum Ether (PE): the yield was calculated by column chromatography separation using ethyl acetate (EtOAc) = 90:10 (vol). And washing the solid catalyst with water, carrying out suction filtration, roasting at 500 ℃ for 5 h, cooling, weighing to obtain the recovery rate, and recycling.
B. Results of the experiment
FIG. 7 shows the change in mass and yield of the catalyst after four cycles. The reaction yield is gradually reduced from the initial 95.1 percent, the second yield is 89.5 percent, the third yield is 83.1 percent, and the final reaction yield is 72.8 percent; the catalyst recovery efficiency also decreased from 91.7% to 70.0%. Thus, it is understood that the reacted Pt/Al2O3The catalyst is changed to a certain extent, so that the catalytic effect is poorer and poorer, and the reaction yield is gradually reduced. It is presumed that the loss and sintering of the active component Pt particles in the catalyst worsen the dispersion of the crystal grains and increase the diameter.
To verify the guess, the original Pt/Al was aligned using a FEI Inc. of America, Tiecnai G2F 20S-Twin, Transmission Electron microscope2O3Supported catalyst and Pt/Al recovered and treated after 1, 3 and 5 times of reaction2O3The catalyst was subjected to microscopic morphology analysis, and the results are shown in fig. 8 to 11.
According to Pt/Al which is not catalyzed by reaction and reacted for 1 time, 3 times and 5 times2O3CatalysisThe TEM images of the reagents clearly show that as the number of reactions increases, the platinum particles in the catalyst become significantly less dispersible and the particle size becomes more and more non-uniform. Further, information on the shape, Size and number of crystal grains can be obtained from TEM photographs, and the average Particle Size and distribution [ PYRZ W D, BUTTREY D J, Particle Size Determination Using TEM: A dispersion of image acquisition and analysis for the same microscopist [ J ] can be obtained by software measurement and calculation in reference literature]. Langmuir, 2008, 24(20) :11350-11360.]Selecting a relatively uniform part in an electron microscope image, and measuring to obtain the platinum particles with the average particle sizes as follows: the average particle size of the primary catalyst is 5.0 nm, the average particle size of the catalyst platinum after one reaction is 5.4 nm, the average particle size of the platinum particles after three reactions is 5.3 nm, and the average particle size of the platinum particles after five reactions is 6.1 nm. The variance of the particle sizes was also calculated to compare the differences between the particle sizes, and the results are shown in FIG. 12.
FIG. 12 is Pt/Al2O3The average particle diameter of platinum particles before and after the catalyst participates in the four reactions, the variance of the platinum particle diameter and the reaction times of the catalyst. After roasting at 500 ℃, carbon deposition of the catalyst is basically removed, black particles in a TEM image are platinum particles loaded on alumina, and the main reason for reducing the activity of the catalyst is the change of platinum grains subjected to reaction at high temperature. It can be seen that the newly prepared Pt/Al2O3The average particle size of platinum particles loaded on the catalyst is 5.0 nm, the dispersibility of the particles is good, and the particles are uniformly distributed; Pt/Al obtained by 1-time reaction and recovery2O3The average particle size of the catalyst is 5.4 nm, the dispersibility of platinum particles is generally good, but the edges of the platinum particles are slightly agglomerated, and the particle size of the catalyst is larger than that of the original catalyst; Pt/Al after 3 times of reaction and recovery2O3The average particle size of the catalyst is further increased to 6.5 nm, and part of platinum particles on the carrier have larger agglomeration and poor dispersibility; Pt/Al subjected to 5 times of reaction and recovered2O3The platinum particles of the catalyst have a wider particle diameter and are poorly dispersed. An increase in the variance of the particle diameter also indicates a deterioration in the effect of dispersing the platinum particles on the carrier.
Pt/Al with good catalytic effect in reaction of ethylene glycol phenylamine2O3The catalytic system of the supported catalyst is researched in a broad spectrum, and the substrate range of substituted aniline is mainly expanded. The result shows that when the electron-donating group exists on the aniline, the reaction yield is higher; when the substituent on aniline is strong electron-withdrawing group or the ortho position of amino group has large group, the reaction yield is low. In testing some naphthylamine substrates, the reaction yield of 2-naphthylamine was found to be the highest, reaching 95%. Gas phase mass spectrum is used together with detection and analysis in the reaction process of 2-naphthylamine and ethylene glycol for synthesizing indole in one step, several possible reaction intermediates and byproducts are presumed, and a possible reaction mechanism is presumed: firstly, glycol is dehydrated under the action of alumina and is converted into acetaldehyde, the acetaldehyde and amino are subjected to aldehyde-amine condensation to remove water, and finally, under the action of metal platinum, dehydrogenation cyclization is carried out to form pyrrole ring, thus completing the reaction process.
In order to increase the utilization efficiency of the noble metal platinum in the catalyst, the catalyst is recycled in several steps. The results show that the catalyst effect is less weakened in the first 4 reactions, and when the reaction times reach 5 times, the yield of the reaction is greatly reduced, which indicates that the catalyst has relatively good stability, can be recycled for 4 times, and the cumulative participation reaction time is 96 hours, but the catalytic effect is not greatly reduced. The microscopic morphology characterization of the original catalyst and the recovered catalyst which respectively undergoes 1, 3 and 5 times of reaction is carried out by an electron microscope, and the result shows that the distribution of platinum particles on the carrier in the original catalyst is relatively uniform, and the distribution and the particle size become disordered along with the increase of the reaction times. It follows from this that: the loss of platinum particles during the reaction process occurs, and the platinum particles are fused and combined into larger particles under the high temperature condition, so that the effective contact area of the catalyst is reduced, which is the main reason for reducing the catalytic efficiency.
Finally, it should be noted that: the above embodiments are only used to illustrate the technical solution of the present invention, and not to limit the same; while the invention has been described in detail and with reference to the foregoing embodiments, it will be understood by those skilled in the art that: the technical solutions described in the foregoing embodiments may still be modified, or some or all of the technical features may be equivalently replaced; and the modifications or the substitutions do not make the essence of the corresponding technical solutions depart from the scope of the technical solutions of the embodiments of the present invention.
Claims (7)
1. A synthetic method of indole derivatives is characterized in that: with acidic Al2O3The Pt/Al loaded Pt is prepared by an impregnation method as a carrier2O3Catalyst, adopting aniline compound, glycol and prepared Pt/Al2O3And (2) carrying out catalytic reaction on a catalyst, controlling the reaction temperature to be 190 ℃, reacting for 24h, adding water and stirring uniformly after the reaction is finished, then extracting with dichloromethane, carrying out rotary evaporation and concentration on an organic phase to remove a solvent, and then carrying out column chromatography separation by using petroleum ether and ethyl acetate as eluents to obtain a target product.
2. The method for synthesizing an indole derivative according to claim 1, wherein: the Pt/Al2O3The preparation method of the catalyst comprises the following steps: firstly, carrying acid carrier Al2O3Placing the mixture in a muffle furnace, roasting the mixture for 4 hours at 500 ℃, and naturally cooling the mixture to room temperature; weighing 1 g of carrier, and soaking in 30 mL of chloroplatinic acid H with the mass concentration of 3%2PtCl6·6H2Stirring the mixture in an O aqueous solution for 24 hours at normal temperature, fully and uniformly mixing reaction liquid, filtering, drying a solid filter cake for 12 hours at 120 ℃, grinding the solid, roasting the ground solid in a muffle furnace for 4 hours at 500 ℃, and naturally cooling to obtain the Pt/Al with the Pt loading of 3wt%2O3A catalyst; the catalyst is activated after being recycled for 4 times: the solid catalyst is washed by water, filtered, roasted for 5 hours at 500 ℃, and cooled for recycling.
3. The method for synthesizing an indole derivative according to claim 1, wherein: the aniline compound is as follows: alkyl-, methoxy-, carbomethoxy-, nitro-or fluorine-substituted anilines, and 1-naphthylamine or 2-naphthylamine.
4. The method for synthesizing an indole derivative according to claim 3, wherein: the aniline compoundThe material is as follows:Nany one of-methylaniline, o-methoxyaniline, m-methoxyaniline, p-methoxyaniline, o-carbomethoxyaniline, m-carbomethoxyaniline, p-carbomethoxyaniline, o-methylaniline, o-tert-butylaniline, o-fluoroaniline, p-fluoroaniline, o-nitroaniline, m-nitroaniline, p-nitroaniline, m-cyanoaniline, p-cyanoaniline, 1-naphthylamine, 2-naphthylamine or 1, 5-diaminonaphthalene.
5. The method for synthesizing indole derivatives according to claim 4, wherein: the aniline compound is as follows: aniline or 2-naphthylamine substituted with an electron donating group.
6. The method for synthesizing an indole derivative according to claim 5, wherein: the aniline compound is 2-naphthylamine.
7. The method for synthesizing an indole derivative according to claim 1, wherein: 1mmol of aniline compound, 54mmol of ethylene glycol and 0.015mmol of catalyst; the column chromatography is eluted according to the volume ratio of petroleum ether to ethyl acetate of 90: 10.
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| CA1150729A (en) * | 1981-04-21 | 1983-07-26 | Mitsui Chemicals Inc. | Process for the preparation of indole and derivatives thereof |
| US4436916A (en) * | 1980-06-03 | 1984-03-13 | Mitsui Toatsu Chemicals, Inc. | Process for the preparation of indoles |
| US4937353A (en) * | 1982-06-24 | 1990-06-26 | Mitsui Toatsu Chemicals, Incorporated | Preparation process for indoles |
| CN111054326A (en) * | 2019-12-26 | 2020-04-24 | 太原理工大学 | Supported catalyst, preparation method thereof and application of supported catalyst in catalyzing synthesis of indole from ethylene glycol and aniline |
-
2021
- 2021-09-07 CN CN202111045501.8A patent/CN113861098A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4436916A (en) * | 1980-06-03 | 1984-03-13 | Mitsui Toatsu Chemicals, Inc. | Process for the preparation of indoles |
| CA1150729A (en) * | 1981-04-21 | 1983-07-26 | Mitsui Chemicals Inc. | Process for the preparation of indole and derivatives thereof |
| US4937353A (en) * | 1982-06-24 | 1990-06-26 | Mitsui Toatsu Chemicals, Incorporated | Preparation process for indoles |
| CN111054326A (en) * | 2019-12-26 | 2020-04-24 | 太原理工大学 | Supported catalyst, preparation method thereof and application of supported catalyst in catalyzing synthesis of indole from ethylene glycol and aniline |
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