CN117720453A - Lignin-based indole derivative synthesis method - Google Patents
Lignin-based indole derivative synthesis method Download PDFInfo
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- CN117720453A CN117720453A CN202311724019.6A CN202311724019A CN117720453A CN 117720453 A CN117720453 A CN 117720453A CN 202311724019 A CN202311724019 A CN 202311724019A CN 117720453 A CN117720453 A CN 117720453A
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- 150000002475 indoles Chemical class 0.000 title claims abstract description 19
- 229920005610 lignin Polymers 0.000 title claims abstract description 16
- 238000001308 synthesis method Methods 0.000 title claims abstract description 7
- 238000006243 chemical reaction Methods 0.000 claims abstract description 43
- 238000000034 method Methods 0.000 claims abstract description 20
- 239000003054 catalyst Substances 0.000 claims abstract description 13
- 229940054051 antipsychotic indole derivative Drugs 0.000 claims abstract description 11
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 claims abstract description 8
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 claims abstract description 7
- 229910052719 titanium Inorganic materials 0.000 claims abstract description 7
- 239000010936 titanium Substances 0.000 claims abstract description 7
- 239000002904 solvent Substances 0.000 claims abstract description 5
- 238000010189 synthetic method Methods 0.000 claims abstract description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 15
- 229940125782 compound 2 Drugs 0.000 claims description 11
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- 239000001257 hydrogen Substances 0.000 claims description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 6
- 229940125904 compound 1 Drugs 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims description 5
- 230000035484 reaction time Effects 0.000 claims description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 4
- 239000004408 titanium dioxide Substances 0.000 claims description 4
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 claims description 4
- RYSXWUYLAWPLES-MTOQALJVSA-N (Z)-4-hydroxypent-3-en-2-one titanium Chemical compound [Ti].C\C(O)=C\C(C)=O.C\C(O)=C\C(C)=O.C\C(O)=C\C(C)=O.C\C(O)=C\C(C)=O RYSXWUYLAWPLES-MTOQALJVSA-N 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- IFMWVBVPVXRZHE-UHFFFAOYSA-M chlorotitanium(3+);propan-2-olate Chemical compound [Cl-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-] IFMWVBVPVXRZHE-UHFFFAOYSA-M 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 238000003756 stirring Methods 0.000 claims description 2
- 230000002194 synthesizing effect Effects 0.000 claims 1
- 239000002994 raw material Substances 0.000 abstract description 6
- 150000001875 compounds Chemical class 0.000 abstract description 4
- 238000003786 synthesis reaction Methods 0.000 abstract description 3
- 238000010438 heat treatment Methods 0.000 abstract 1
- 239000003446 ligand Substances 0.000 abstract 1
- 239000000047 product Substances 0.000 description 24
- -1 1-phenyl-2- (2-methoxyphenyl) -propane-1, 3-diol Chemical compound 0.000 description 14
- 238000004896 high resolution mass spectrometry Methods 0.000 description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- 238000005481 NMR spectroscopy Methods 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 150000003233 pyrroles Chemical class 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000007810 chemical reaction solvent Substances 0.000 description 3
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 3
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 238000010626 work up procedure Methods 0.000 description 3
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 150000001555 benzenes Chemical group 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 238000006352 cycloaddition reaction Methods 0.000 description 2
- LHGVFZTZFXWLCP-UHFFFAOYSA-N guaiacol Chemical compound COC1=CC=CC=C1O LHGVFZTZFXWLCP-UHFFFAOYSA-N 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- ADVORQMAWLEPOI-XHTSQIMGSA-N (e)-4-hydroxypent-3-en-2-one;oxotitanium Chemical compound [Ti]=O.C\C(O)=C/C(C)=O.C\C(O)=C/C(C)=O ADVORQMAWLEPOI-XHTSQIMGSA-N 0.000 description 1
- OUKQTRFCDKSEPL-UHFFFAOYSA-N 1-Methyl-2-pyrrolecarboxaldehyde Chemical class CN1C=CC=C1C=O OUKQTRFCDKSEPL-UHFFFAOYSA-N 0.000 description 1
- VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 1
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- 229910010413 TiO 2 Inorganic materials 0.000 description 1
- CUJRVFIICFDLGR-UHFFFAOYSA-N acetylacetonate Chemical compound CC(=O)[CH-]C(C)=O CUJRVFIICFDLGR-UHFFFAOYSA-N 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 150000001345 alkine derivatives Chemical class 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 125000000609 carbazolyl group Chemical class C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 229960001867 guaiacol Drugs 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000005917 in vivo anti-tumor Effects 0.000 description 1
- 238000003402 intramolecular cyclocondensation reaction Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000007243 oxidative cyclization reaction Methods 0.000 description 1
- FDPIMTJIUBPUKL-UHFFFAOYSA-N pentan-3-one Chemical class CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Abstract
The invention discloses a synthesis method of lignin-based indole derivatives, and belongs to the technical field of organic synthesis. The method takes lignin beta-O-4 model compound and N-methyl pyrrole-2-vinyl ketone compound as reaction raw materials, and under the action of a titanium catalyst and a 1,10 phenanthroline ligand, the lignin beta-O-4 model compound and the N-methyl pyrrole-2-vinyl ketone compound react for a certain time in a solvent in a heating way under the air atmosphere, and finally the lignin-based indole derivative is obtained. The synthetic method for preparing the indole derivative has the advantages of green and renewable raw materials, simple operation, mild reaction conditions, high product selectivity and the like, and provides a green new way for preparing indole compounds.
Description
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to a synthesis method of lignin-based indole derivatives.
Background
Indole and its derivatives are important fine chemical raw materials and chemical products, and have very wide important application in the fields of industry, agriculture, medicine and the like. Indole compounds are used as an important heterocyclic compound and have wide biological activity. Patents (CN 101516366) and (CN 102307868 a) report that various indole derivatives show excellent in vitro activity and excellent in vivo antitumor effects. The synthesis of indole derivatives has been receiving extensive attention from chemists due to their remarkable biopharmaceutical activity and unique plastic structure.
Currently, there are a number of methods for the preparation of indole derivatives (Chem.Rev., 2012,112,3508;Chem.Rev, 2006,106,2875). Among them, the method for preparing indole derivatives by construction of benzene ring from pyrrole derivatives is one of the ways for rapidly and effectively obtaining indole derivatives with various structures, and the related preparation method comprises the following steps: 1) Intramolecular cyclization of functionalized pyrrole derivatives (j.am. Chem. Soc.2006,128, 7436); 2) Intermolecular cycloaddition of functionalized pyrroles with olefins (j.org.chem.2006, 71,5249); 3) Cycloaddition of pyrrole with diazoenone (angelw.chem.int.ed.2014, 53,4076); 4) Oxidative cyclization of pyrrole derivatives with two molecules of alkyne or β -chloroketone (j.org. chem.2009,74,7481; org.chem. Front.2015,2,1361). However, these methods have limitations such as non-renewable raw materials, relatively low yields, complicated operations, and the like. The research and development of a novel, efficient, low-energy, environment-friendly, convenient to operate and green synthetic method of indole derivatives has important significance.
Disclosure of Invention
In order to solve the problems in the prior art, the invention aims to provide a method for preparing indole derivatives by using lignin model compounds, which has the advantages of green and renewable raw materials, simple operation, mild reaction conditions, high product selectivity and the like, and provides a green new way for preparing indole compounds.
The invention aims at realizing the following steps:
the synthesis method of the lignin-based indole derivative mainly comprises the following steps: adding lignin beta-O-4 model compound 1, N-methylpyrrole-2-vinyl ketone compound 2, titanium catalyst and 1, 10-phenanthroline into a solvent, stirring and reacting for a certain time in an air atmosphere, and separating and purifying to obtain carbazole derivative 3; the reaction general formula is:
the R is 1 And R is 2 Is alkyl, alkoxy or hydrogen with 1-3 carbon atoms; r is R 3 Is alkyl with 1-3 carbon atoms, substituted benzene ring, aromatic heterocycle or hydrogen; r is R 4 Is methyl or hydrogen.
Further, in the above technical scheme, the titanium catalyst is one or more than two of titanium tetrachloride, titanium dioxide, titanium acetylacetonate and triisopropoxy titanium chloride.
Further, in the above technical scheme, the solvent is one or more of toluene, 1, 4-dioxane, acetonitrile, ethanol, isopropanol, dimethyl sulfoxide and dimethylformamide.
Further, in the above technical scheme, the reaction conditions are as follows: the temperature is controlled at 30-150 ℃ and the reaction time is 2-24h.
Further, in the above technical scheme, the molar ratio of the lignin beta-O-4 model compound 1 to the N-methylpyrrole-2-vinyl ketone compound 2 is 1:1 to 5:1, preferably 2:1 to 4:1; the molar ratio of the titanium catalyst to the N-methylpyrrole-2-vinyl ketone compound 2 is 0.01:1-0.3:1, and the preferred molar ratio is 0.05:1-0.2:1; the molar ratio of the 1, 10-phenanthroline to the N-methylpyrroline-2-vinyl ketone compound 2 is 0.015:1-0.45:1, and the preferred molar ratio is 0.015:1-0.3:1.
Further, in the above technical scheme, lignin β -O-4 model compound 1 is selected from 1-phenyl-2- (2-methoxyphenyl) -propane-1, 3-diol (1 a), 1- (4-methoxyphenyl) -2- (2-methoxyphenyl) -propane-1, 3-diol (1 b); n-methylpyrrolidine-2-vinyl ketone compound 2 is selected from N-methylpyrrolidine-2-phenyl vinyl ketone (2 a), N-methylpyrrolidine-2- (4-methylphenyl) vinyl ketone (2 b), N-methylpyrrolidine-2- (4-chlorophenyl) vinyl ketone (2 c), N-methylpyrrolidine-2-furyl vinyl ketone (2 d), and N-methylpyrrolidine-2-cyclopropenyl vinyl ketone (2 e).
The synthetic method for preparing the indole compound has the advantages of green and renewable raw materials, simple operation, mild reaction conditions, high product selectivity and the like, and provides a green new way for preparing the indole compound.
Drawings
In order to more clearly illustrate the embodiments of the present invention, the drawings to which the embodiments relate will be briefly described.
FIG. 1 is a schematic illustration of 1-methyl-4, 6-dibenzoyl indole prepared in example 1 1 H-NMR nuclear magnetic pattern.
FIG. 2 is a schematic illustration of 1-methyl-4- (4-methoxy) benzoyl-6-benzoylindole prepared in example 9 1 H-NMR nuclear magnetic pattern.
FIG. 3 is a schematic illustration of 1, 2-dimethyl-4, 6-dibenzoyl indole prepared in example 14 1 H-NMR nuclear magnetic pattern.
Detailed Description
Lignin beta-O-4 model Compound 1 was prepared according to the literature (Green chem.2023,25, 550-553), N-methylpyrrole-2-vinyl ketone Compound 2 preparation method: commercially available ethyl ketone derivative A (1 mmol), N-methylpyrrole-2-carbaldehyde derivative B (1 mmol) and NaOH (3 mmol) were added to 5ml of ethanol and the reaction stirred at room temperature for 20h. After stopping the reaction, the ethanol is distilled off under reduced pressure, and the N-methylpyrrole-2-vinyl ketone compound 2 is obtained by column chromatography. The reaction formula is:
the R is 3 Is alkyl with 1-3 carbon atoms, substituted benzene ring, aromatic heterocycle or hydrogen; r is R 4 Is methyl or hydrogen. Compounds A and B were purchased from Beijing enokid.
The following detailed description of the invention is provided in connection with examples, but the implementation of the invention is not limited thereto, and it is obvious that the examples described below are only some examples of the invention, and that it is within the scope of protection of the invention to those skilled in the art to obtain other similar examples without inventive faculty.
Example 1:
1-phenyl-2- (2-methoxyphenyl) -propane-1, 3-diol 1a (110 mg,0.4 mmol), N-methylpyrrole-2-phenylvinyl ketone 2a (42 mg,0.2 mmol), titanium tetrachloride TiCl 4 The catalyst (3.8 mg,10 mol%) and 1, 10-phenanthroline (5.4 mg,15 mol%) were added to 5mL of acetonitrile, and the mixture was heated to 120℃under air conditions and stirred for 16 hours to react according to the following reaction scheme. After cooling to room temperature, the mixture was filtered through celite, 20mL of water was added to the filtrate, and the aqueous phase (2X 15 mL) was extracted with methylene chloride to separate the organic phase. The organic phase was mixed, dried over anhydrous magnesium sulfate and filtered. The volatile components were removed under reduced pressure, and then separated by column chromatography on silica gel (petroleum ether (60-90 ℃ C.)/ethyl acetate/dichloromethane, v/v/v=250:8:20) to give product 3a (51 mg, yield 75%) as a yellow solid, guaiacol 4a (45 mg, yield 92%). The target product is confirmed by nuclear magnetic resonance spectrum and high resolution mass spectrometry determination, 3a 1 The H-NMR nuclear magnetic characterization is shown in FIG. 1.
Example 2
The reaction procedure and operation were the same as in example 1, except that the catalyst was titanium dioxide TiO 2 (4.8 mg,30 mol%), 1, 10-phenanthroline (16 mg,45 mol%). The reaction was stopped, and the desired product 3a (17 mg, yield 25%) was obtained by working up. Titanium dioxide is also described as a catalyst for the reaction, but is less effective than titanium tetrachloride.
Example 3
The procedure and operation were the same as in example 1, except that the catalyst was titanium acetylacetonate TiO (acac) 2 (0.5 mg,1 mol%), 1, 10-phenanthroline (0.5 mg,1.5 mol%). The reaction was stopped, and the desired product 3a (13 mg, yield 19%) was obtained by working up. It is explained that titanyl acetylacetonate may also be used as a catalyst for the reaction, but is not the optimal catalyst.
Example 4
The reaction procedure and operation were the same as in example 1, except that toluene was used as the reaction solvent, the reaction temperature was 140℃and the reaction time was 24 hours. The reaction was stopped, and the desired product 3a (53 mg, yield 78%) was obtained by working up.
Example 5
The reaction procedure and operation were the same as in example 1, except that the reaction solvent was dimethyl sulfoxide, the reaction temperature was 150℃and the reaction time was 2 hours. The reaction was stopped, and the desired product 3a (10 mg, yield 15%) was obtained by working up.
Example 6
The reaction procedure and operation were the same as in example 1, except that the reaction solvent was ethanol, the reaction temperature was 30℃and the reaction time was 12 hours. The reaction was stopped, and the desired product 3a (13 mg, yield 20%) was obtained by working up.
Example 7
The procedure was as in example 4, except that 1-phenyl-2- (2-methoxyphenyl) -propane-1, 3-diol 1a (55 mg,0.2 mmol) was added and the reaction was stopped, followed by work-up to give the desired product 3a (31 mg, yield 46%). Indicating that reducing the amount of 1a is detrimental to the reaction.
Example 8
The procedure was as in example 4, except that 1-phenyl-2- (2-methoxyphenyl) -propane-1, 3-diol 1a (275 mg,1.0 mmol) was added and the reaction was stopped, followed by work-up to give the desired product 3a (50 mg, yield 76%). It was demonstrated that further increases in 1a had little effect on the reaction.
Example 9
The procedure was as in example 4, except that 1- (4-methoxyphenyl) -2- (2-methoxyphenyl) -propane-1, 3-diol 1b (122 mg,0.4 mmol) was added to the reaction system. The reaction was stopped, and the desired product 3b (50 mg, yield 68%) was obtained as a pale yellow solid by post-treatment. The target product is confirmed by nuclear magnetic resonance spectroscopy and high resolution mass spectrometry.
Example 10
The procedure was as in example 4, except that 2-alkenylpyrrole derivative 2b (45 mg,0.2 mmol) was added to the reaction system. The reaction was stopped, and the desired product 3c (53 mg, yield 75%) was obtained as a pale yellow solid by post-treatment. The target product is confirmed by nuclear magnetic resonance spectroscopy and high resolution mass spectrometry.
Example 11
The procedure was as in example 4, except that 2-alkenylpyrrole derivative was added to the reaction system as 2c (49 mg,0.2 mmol). The reaction was stopped, and the desired product was obtained as a white solid by working up 3d (54 mg, yield 72%). The target product is confirmed by nuclear magnetic resonance spectroscopy and high resolution mass spectrometry.
Example 12
The procedure was as in example 4, except that 2-alkenylpyrrole derivative was added to the reaction system in 2d (40 mg,0.2 mmol). The reaction was stopped, and the desired product 3e (44 mg, yield 67%) was obtained as a pale yellow solid by post-treatment. The target product is confirmed by nuclear magnetic resonance spectroscopy and high resolution mass spectrometry.
Example 13
The procedure was as in example 4, except that 2-alkenylpyrrole derivative was added to the reaction system as 2e (35 mg,0.2 mmol). The reaction was stopped and the desired product 3f (34 mg, yield 56%) was obtained as a pale yellow oily liquid after work-up. The target product is confirmed by nuclear magnetic resonance spectroscopy and high resolution mass spectrometry.
Example 14
The procedure was as in example 4, except that 2-alkenylpyrrole derivative was added to the reaction system as 2f (45 mg,0.4 mmol). The reaction was stopped, and the desired product was obtained as a white solid (3 g, 48mg, yield 68%). The target product is confirmed by nuclear magnetic resonance spectroscopy and high resolution mass spectrometry.
Finally, it should be noted that: the above embodiments are only for illustrating the technical solution of the present invention, and not for limiting the same; although the invention has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: the technical scheme described in the foregoing embodiments can be modified or some or all of the technical features thereof can be replaced by equivalents; such modifications and substitutions do not depart from the spirit of the invention.
Claims (5)
1. A method for synthesizing lignin-based indole derivatives is characterized in that: adding lignin beta-O-4 model compound 1, N-methylpyrrole-2-vinyl ketone compound 2, titanium catalyst and 1,10 phenanthroline into a solvent, stirring and reacting for a certain time in an air atmosphere, and separating and purifying to obtain indole derivatives 3; the reaction formula is:
r in the reaction formula 1 And R is 2 Is alkyl, alkoxy or hydrogen with 1-3 carbon atoms; r is R 3 Is alkyl with 1-3 carbon atoms, substituted benzene ring, aromatic heterocycle or hydrogen; r is R 4 Is methyl or hydrogen.
2. The synthesis method according to claim 1, wherein the titanium catalyst is one or more of titanium tetrachloride, titanium dioxide, titanium acetylacetonate, and titanium triisopropoxide chloride.
3. The method according to claim 1, wherein the solvent is one or more of toluene, 1, 4-dioxane, acetonitrile, ethanol, isopropanol, dimethyl sulfoxide, and dimethylformamide.
4. The synthetic method of claim 1 wherein the reaction conditions are: the temperature is controlled at 30-150 ℃ and the reaction time is 2-24h.
5. The synthesis method according to claim 1, wherein the molar ratio of lignin beta-O-4 model compound 1 to N-methylpyrrole-2-vinyl ketone compound 2 is 1:1-5:1; the molar ratio of the titanium catalyst to the N-methylpyrrole-2-vinyl ketone compound 2 is 0.01:1-0.3:1; the molar ratio of the 1, 10-phenanthroline to the N-methylpyrrole-2-vinyl ketone compound 2 is 0.015:1-0.045:1.
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