CN115745825A - Method for catalyzing amide alkylation reaction by using tridentate NNO nickel complex - Google Patents
Method for catalyzing amide alkylation reaction by using tridentate NNO nickel complex Download PDFInfo
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- 238000005804 alkylation reaction Methods 0.000 title claims abstract description 41
- 150000001408 amides Chemical class 0.000 title claims abstract description 35
- 238000000034 method Methods 0.000 title claims abstract description 26
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 title abstract description 35
- 229910052759 nickel Inorganic materials 0.000 title abstract description 13
- 238000006243 chemical reaction Methods 0.000 claims abstract description 110
- -1 alcohol compound Chemical class 0.000 claims abstract description 20
- 239000012295 chemical reaction liquid Substances 0.000 claims abstract description 9
- 239000007810 chemical reaction solvent Substances 0.000 claims abstract description 8
- 239000003513 alkali Substances 0.000 claims abstract description 4
- 238000002156 mixing Methods 0.000 claims abstract description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 171
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 31
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 18
- 239000007864 aqueous solution Substances 0.000 claims description 18
- 239000007788 liquid Substances 0.000 claims description 18
- ZRLVQFQTCMUIRM-UHFFFAOYSA-N potassium;2-methylbutan-2-olate Chemical group [K+].CCC(C)(C)[O-] ZRLVQFQTCMUIRM-UHFFFAOYSA-N 0.000 claims description 18
- 238000000926 separation method Methods 0.000 claims description 17
- 125000000923 (C1-C30) alkyl group Chemical group 0.000 claims description 14
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
- 125000003118 aryl group Chemical group 0.000 claims description 10
- 150000001875 compounds Chemical class 0.000 claims description 9
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 claims description 8
- 125000005842 heteroatom Chemical group 0.000 claims description 8
- 229910052760 oxygen Inorganic materials 0.000 claims description 8
- 229910052717 sulfur Inorganic materials 0.000 claims description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims description 7
- 239000002994 raw material Substances 0.000 claims description 7
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 6
- 239000002585 base Substances 0.000 claims description 5
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 claims description 4
- 238000001035 drying Methods 0.000 claims description 4
- 239000003480 eluent Substances 0.000 claims description 4
- 238000001704 evaporation Methods 0.000 claims description 4
- 229910052744 lithium Inorganic materials 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound 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 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 2
- CUJRVFIICFDLGR-UHFFFAOYSA-N acetylacetonate Chemical compound CC(=O)[CH-]C(C)=O CUJRVFIICFDLGR-UHFFFAOYSA-N 0.000 claims description 2
- 229910052783 alkali metal Inorganic materials 0.000 claims description 2
- 150000001340 alkali metals Chemical group 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 238000001816 cooling Methods 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- 238000007865 diluting Methods 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 125000001072 heteroaryl group Chemical group 0.000 claims description 2
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 2
- 239000011261 inert gas Substances 0.000 claims description 2
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 claims description 2
- SKTCDJAMAYNROS-UHFFFAOYSA-N methoxycyclopentane Chemical compound COC1CCCC1 SKTCDJAMAYNROS-UHFFFAOYSA-N 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 239000012046 mixed solvent Substances 0.000 claims description 2
- 125000001624 naphthyl group Chemical group 0.000 claims description 2
- 239000012074 organic phase Substances 0.000 claims description 2
- 239000003208 petroleum Substances 0.000 claims description 2
- 239000012071 phase Substances 0.000 claims description 2
- 229910052700 potassium Inorganic materials 0.000 claims description 2
- IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 claims description 2
- 229910052708 sodium Inorganic materials 0.000 claims description 2
- 239000011734 sodium Substances 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- SRCZQMGIVIYBBJ-UHFFFAOYSA-N ethoxyethane;ethyl acetate Chemical compound CCOCC.CCOC(C)=O SRCZQMGIVIYBBJ-UHFFFAOYSA-N 0.000 claims 1
- 238000010898 silica gel chromatography Methods 0.000 claims 1
- 239000000758 substrate Substances 0.000 abstract description 21
- 239000003054 catalyst Substances 0.000 abstract description 5
- 230000015572 biosynthetic process Effects 0.000 abstract description 3
- 238000003786 synthesis reaction Methods 0.000 abstract description 3
- 229910052723 transition metal Inorganic materials 0.000 abstract description 2
- 150000003624 transition metals Chemical class 0.000 abstract description 2
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 96
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 52
- 239000000047 product Substances 0.000 description 37
- 235000019445 benzyl alcohol Nutrition 0.000 description 32
- 239000000243 solution Substances 0.000 description 26
- 239000012298 atmosphere Substances 0.000 description 18
- 238000004440 column chromatography Methods 0.000 description 17
- 238000012512 characterization method Methods 0.000 description 16
- 239000007858 starting material Substances 0.000 description 16
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 15
- 238000005160 1H NMR spectroscopy Methods 0.000 description 15
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 229910052799 carbon Inorganic materials 0.000 description 5
- KDISMIMTGUMORD-UHFFFAOYSA-N 1-acetylpiperidine Chemical compound CC(=O)N1CCCCC1 KDISMIMTGUMORD-UHFFFAOYSA-N 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- PMDCZENCAXMSOU-UHFFFAOYSA-N N-ethylacetamide Chemical compound CCNC(C)=O PMDCZENCAXMSOU-UHFFFAOYSA-N 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- 230000029936 alkylation Effects 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- LVUQCTGSDJLWCE-UHFFFAOYSA-N 1-benzylpyrrolidin-2-one Chemical compound O=C1CCCN1CC1=CC=CC=C1 LVUQCTGSDJLWCE-UHFFFAOYSA-N 0.000 description 2
- RSQUAQMIGSMNNE-UHFFFAOYSA-N 1-methyl-3h-indol-2-one Chemical compound C1=CC=C2N(C)C(=O)CC2=C1 RSQUAQMIGSMNNE-UHFFFAOYSA-N 0.000 description 2
- JMVIVASFFKKFQK-UHFFFAOYSA-N 1-phenylpyrrolidin-2-one Chemical compound O=C1CCCN1C1=CC=CC=C1 JMVIVASFFKKFQK-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- WRAGCBBWIYQMRF-UHFFFAOYSA-N N-Cyclohexylacetamide Chemical compound CC(=O)NC1CCCCC1 WRAGCBBWIYQMRF-UHFFFAOYSA-N 0.000 description 2
- OHLUUHNLEMFGTQ-UHFFFAOYSA-N N-methylacetamide Chemical compound CNC(C)=O OHLUUHNLEMFGTQ-UHFFFAOYSA-N 0.000 description 2
- ZWXPDGCFMMFNRW-UHFFFAOYSA-N N-methylcaprolactam Chemical compound CN1CCCCCC1=O ZWXPDGCFMMFNRW-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
- 239000002168 alkylating agent Substances 0.000 description 2
- 229940100198 alkylating agent Drugs 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 238000001212 derivatisation Methods 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- QNLOWBMKUIXCOW-UHFFFAOYSA-N indol-2-one Chemical compound C1=CC=CC2=NC(=O)C=C21 QNLOWBMKUIXCOW-UHFFFAOYSA-N 0.000 description 2
- FGFUBBNNYLNVLJ-UHFFFAOYSA-N indolone Natural products C1=CC=C2C(=O)C=NC2=C1 FGFUBBNNYLNVLJ-UHFFFAOYSA-N 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- AJFDBNQQDYLMJN-UHFFFAOYSA-N n,n-diethylacetamide Chemical compound CCN(CC)C(C)=O AJFDBNQQDYLMJN-UHFFFAOYSA-N 0.000 description 2
- UXDAWVUDZLBBAM-UHFFFAOYSA-N n,n-diethylbenzeneacetamide Chemical compound CCN(CC)C(=O)CC1=CC=CC=C1 UXDAWVUDZLBBAM-UHFFFAOYSA-N 0.000 description 2
- PZYDAVFRVJXFHS-UHFFFAOYSA-N n-cyclohexyl-2-pyrrolidone Chemical compound O=C1CCCN1C1CCCCC1 PZYDAVFRVJXFHS-UHFFFAOYSA-N 0.000 description 2
- PDUSWJORWQPNRP-UHFFFAOYSA-N n-propan-2-ylacetamide Chemical compound CC(C)NC(C)=O PDUSWJORWQPNRP-UHFFFAOYSA-N 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000007789 sealing Methods 0.000 description 2
- 150000003334 secondary amides Chemical class 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 150000003511 tertiary amides Chemical class 0.000 description 2
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 description 1
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 description 1
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 1
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229910017052 cobalt Inorganic materials 0.000 description 1
- 239000010941 cobalt Substances 0.000 description 1
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 1
- FDPIMTJIUBPUKL-UHFFFAOYSA-N dimethylacetone Natural products CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 229910052741 iridium Inorganic materials 0.000 description 1
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 description 1
- 229910052748 manganese Inorganic materials 0.000 description 1
- 239000011572 manganese Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 229910052707 ruthenium Inorganic materials 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a method for catalyzing amide alkylation reaction by using a tridentate NNO nickel complex, which comprises the following steps: in an inert gasUnder the protection of a catalyst, mixing an alcohol compound (III), an amide compound (IV), alkali, a tridentate NNO-Ni complex (I) and a reaction solvent, reacting for 8-48 h at 110-150 ℃, and then carrying out post-treatment on reaction liquid to obtain a product alkylated amide (V); the method has the advantages of cheap transition metal nickel, stable complex, simple operation, wide application range of reaction substrates, high reaction selectivity and important value in synthesis;
Description
Technical Field
The invention relates to a derivatization method of an amide compound, in particular to a method for catalyzing C-alkylation reaction of alcohol and amide by using a novel tridentate NNO nickel complex.
Background
Amides are important organic compounds and are widely used in the fields of pesticides, medicines, materials and the like. Derivatization of amides is an important means for obtaining amides. Among these, the C-alkylation of amides is one of the important types of conversion.
The traditional amide alkylation reaction uses halogenated hydrocarbon as an alkylation reagent, and has the problems of environment-unfriendly reaction raw materials, generation of a large amount of inorganic salt byproducts, low selectivity and the like.
In recent years, the carbon alkylation reaction of amides by hydrogen catalyzed reaction with alcohols as alkylating agents has been receiving much attention. In this conversion, the alcohol source is extensive and water is the only by-product. Therefore, the C-alkylation reaction of alcohol and amide conforms to the green and sustainable green chemical concept. Currently, many reports are made of amide carbon alkylation reactions catalyzed by noble metals such as iridium and ruthenium, but the catalysts are expensive and the ligands are complex. There is an urgent need to develop inexpensive metal-catalyzed amide carbon alkylation reaction systems.
The amide alkylation reaction of cheap metals such as cobalt, nickel and manganese has been reported. These reported methods still have some problems, such as: 1. the monodentate or tridentate phosphine ligand is used, the ligand synthesis steps are complex and unstable, and the reaction operation is sensitive; 2. most catalytic systems are only compatible with tertiary amides, especially acetyl tertiary amides (Chemical Communications 2020,56, 14083-14086). Substrates of secondary amides, however, suffer from selectivity problems for C or N alkylation; 3. it is incompatible with inert alcohols such as methanol or ethanol.
Therefore, there is a strong need in the art to develop novel, stable, inexpensive metal complexes that achieve C-alkylation of alcohols with amides with good substrate compatibility. The invention develops a novel NNO nickel complex, is applied to the C-alkylation reaction of alcohol and amide, and has the advantages of stable catalyst, simple operation, wide substrate compatibility and the like.
Disclosure of Invention
The invention aims to provide a method for realizing amide carbon alkylation by using alcohol as an alkylating agent by using a novel nickel complex.
The technical scheme of the invention is as follows:
a process for catalyzing the C-alkylation of an alcohol with an amide using a tridentate NNO-Ni complex, the process comprising:
under the protection of inert gas, mixing an alcohol compound (III), an amide compound (IV), alkali, a tridentate NNO-Ni complex (I) and a reaction solvent, reacting for 8-48 h at 110-150 ℃, and then carrying out post-treatment on reaction liquid to obtain a product alkylated amide (V);
the mass ratio of the alcohol compound (III), the amide compound (IV), the alkali and the tridentate NNO-Ni complex (I) is 1:3 to 10:1.5 to 3.0:0.05 to 0.2, preferably 1:4.5:1.5:0.1;
the base is R 5 OM or bis (trimethylsilyl) amino potassium/sodium/lithium; at R 5 In OM, R 5 Is H or C1-C10 alkyl, preferably C1-C5 alkyl, more preferably tert-amyl; m is an alkali metal Li, na or K, preferably K; particularly preferably, the base is potassium tert-amylate;
the reaction solvent includes but is not limited to one or a mixture of two or more of toluene, tetrahydrofuran, anisole, cyclopentyl methyl ether, 1, 4-dioxane, n-heptane and dimethyl ether in any proportion, such as: a mixed solvent of toluene and tetrahydrofuran and toluene and dimethyl ether, preferably toluene is used as a reaction solvent;
the volume mol ratio of the reaction solvent to the alcohol is 0-4: 1mL/mmol, preferably 2:1mL/mmol;
the post-treatment method comprises the following steps: after the reaction is finished, cooling the reaction liquid to room temperature, diluting the reaction liquid with toluene, adjusting the pH value to 8-9 with saturated sodium bicarbonate aqueous solution, separating liquid, extracting the water phase with toluene, combining organic phases, concentrating, and separating by silica gel (200-300 meshes) column chromatography, wherein the volume ratio of petroleum ether to ethyl acetate is 10:1 as eluent, collecting the eluent containing the target compound, evaporating the solvent and drying to obtain the product alkylated amide (V);
the structural formulas of the raw material alcohol compound (III), the amide compound (IV) and the product alkylated amide (V) are as follows:
in the formulae (III), (IV), (V),
R 6 is H or C1-C30 alkyl, C3-C7 cycloalkyl, naphthyl, heteroaryl, phenyl or substituted phenyl, wherein the phenyl ring of the substituted phenyl is substituted by one or more substituents which are respectively and independently C1-C30 alkyl, C1-C30 alkoxy, phenyl, hydroxymethyl, halogen or halogenated methyl;
R 7 is H or phenyl;
R 8 is H, C1-C30 alkyl, C6-C30 aryl, or C1-C30 alkyl or C6-C30 aryl containing one or more heteroatoms selected from O, S or N;
R 9 、R 10 each independently is H, C1-C30 alkyl, C6-C30 aryl, or C1-C30 alkyl or C6-C30 aryl containing one or more heteroatoms selected from O, S or N;
or, R 8 、R 9 And the groups therebetween, together form a ring, with or without one or more heteroatoms independently selected from O, S, or N in the ring;
or, R 9 、R 10 And N therebetween, together form a ring with or without one or more heteroatoms independently selected from O, S or N.
As will be appreciated by those skilled in the art, the term "secondary amide" as used herein refers to a compound obtained by substituting one hydrogen on N in an amide. Similarly, the term "tertiary amide" as used herein refers to a compound resulting from the substitution of both hydrogens on the N in the amide.
The structural formula of the tridentate NNO-Ni complex used in the method is as follows:
in the formula (I), the compound is shown in the specification,
R 1 、R 2 、R 3 、R 4 each independently is H, C1-C30 alkyl or C6-C30 aryl;
x is F, cl, br, I, OAc, acac or OTf;
n＝0～2。
particularly preferably, the tridentate NNO-Ni complex has the following structural formula:
the preparation method of the tridentate NNO-Ni complex shown in the formula (I) comprises the following steps:
dropwise adding an alcohol solution of the compound (I-a) to the NiX under an inert atmosphere 2 Stirring the mixture for 10 hours at room temperature (20-30 ℃), and then carrying out post-treatment on the reaction solution to obtain a tridentate NNO-Ni complex (I);
the compound (I-a) and NiX 2 The ratio of the amounts of substances (1): 0.80 to 0.95, preferably 1:0.90;
alcoholic solution of the compound (I-a), niX 2 The alcohol solution of (1) is selected from methanol, ethanol, isopropanol or butanol;
the post-treatment method comprises the following steps: after the reaction is finished, evaporating the solvent of the reaction solution, redissolving the reaction solution by using ethanol, dropwise adding the redissolved reaction solution into methyl tert-butyl ether (MTBE), stirring the redissolved reaction solution, separating out a green powder solid, centrifuging, washing and drying the solid to obtain a tridentate NNO-Ni complex (I);
formula (I-a), niX 2 In (1),
R 1 、R 2 、R 3 、R 4 、nand X is as defined in formula (I).
The invention has the following beneficial effects:
the invention provides a method for nickel-catalyzed C-alkylation of alcohol with amide. Compared with the existing method, the method has the advantages of cheap transition metal nickel, stable complex, simple operation, wide application range of reaction substrates, high reaction selectivity and important value in synthesis.
Detailed Description
The invention is further described below by means of specific examples, without the scope of protection of the invention being limited thereto.
The catalyst complex II used in the following examples has the formula:
the synthesis method of the catalyst II comprises the following steps:
raw materials:
NiCl 2 (DME)
under an inert atmosphere, 10mL of an ethanol solution of 464mg of 2- - ((N, N-diethylamino) methyl) -tetrahydroquinolin-8-one was added dropwise to 368mg of NiCl 2 To 15mL of an ethanol solution of (DME), the mixture was stirred at room temperature for 10 hours. After the reaction is finished, the solvent is removed from the reaction liquid by evaporation, the reaction liquid is redissolved by 5mL of ethanol and then is dripped into 50mL of MTBE for stirring, a green powder product is obviously seen in the MTBE, the mixture is centrifuged, the MTBE is repeatedly centrifuged after being washed, and the green product Ni-1 is obtained after drying, wherein the yield is 89%.
Example 1: nickel-catalyzed C-alkylation of benzyl alcohol with N-methylacetamide:
Under an inert atmosphere, II (54mg, 15mol%) was added to the reaction tube, and the reaction tube was transferred to a glove box, and potassium tert-amylate (379mg, 3mmol), starting benzyl alcohol (104. Mu.L, 1 mmol), substrate N-methylacetamide (261mg, 3mmol) and toluene (2 mL) were sequentially added, and the reaction tube was sealed and transferred to the glove box. Reacting for 24 hours in an oil bath at 150 ℃, after the reaction is finished, adding 5mL of toluene to fully dissolve a reaction solution when a reaction system is cooled to room temperature, adjusting the pH to about 8-9 by using a saturated sodium bicarbonate aqueous solution, separating liquid, extracting toluene, concentrating, and performing column chromatography separation to finally obtain a product 134mg, wherein the yield is as follows: 82 percent. Product characterization data are as follows: 1 H NMR(500MHz,CDCl 3 )δ7.30–7.27(m,2H),7.20–7.17(m,3H),5.51(s,1H),2.95(t,J＝7.5Hz,2H),2.76(d,J＝4.8Hz,2H),2.46(t,J＝7.5Hz,2H). 13 C NMR(125MHz,CDCl 3 )δ172.73,140.95,128.51,128.31,126.21,38.41,31.75,26.27.
example 2: nickel-catalyzed C-alkylation of benzyl alcohol with N-ethylacetamide:
Under an inert atmosphere, II (54mg, 15mol%) was added to the reaction tube, and the reaction tube was transferred to a glove box, followed by addition of potassium tert-amylate (379mg, 3mmol), starting benzyl alcohol (104. Mu.L, 1 mmol), substrate N-ethylacetamide (219mg, 3mmol) and toluene (2 mL), followed by sealing and transfer to the glove box. Reacting for 24 hours in an oil bath at 150 ℃, after the reaction is finished, adding 5mL of toluene to fully dissolve a reaction solution when a reaction system is cooled to room temperature, adjusting the pH to about 8-9 by using a saturated sodium bicarbonate aqueous solution, separating liquid, extracting toluene, concentrating, and performing column chromatography separation to finally obtain a product of 142mg, wherein the yield is as follows: 80 percent. Product characterization data are as follows: 1H NMR (500MHz, CDCl3) delta 7.29-7.25 (m, 2H), 7.19-7.17 (m, 3H), 5.66 (s, 1H), 3.25-3.20 (m, 2H), 2.94 (t, J =7.3Hz, 2H), 2.44 ((t, J =7.3Hz, 2H), 1.05 (t, J =7.3Hz, 3H), 13C NMR (125MHz, CDCl3) delta 171.99,140.97,128.56,128.26,126.18,38.52,34.57,34.31,31.81,14.82.
Example 3: nickel-catalyzed C-alkylation of benzyl alcohol with N-isopropyl acetamide:
Under an inert atmosphere, II (54mg, 15mol%) was added to the reaction tube, which was transferred to a glove box, and potassium tert-amylate (379mg, 3mmol), starting benzyl alcohol (104. Mu.L, 1 mmol), N-isopropylacetamide (303mg, 3mmol) as a substrate, and toluene (2 mL) were sequentially added thereto, followed by sealing and transferring out of the glove box. Reacting for 24 hours in an oil bath at 150 ℃, after the reaction is finished, adding 5mL of toluene to fully dissolve a reaction solution when a reaction system is cooled to room temperature, adjusting the pH to about 8-9 by using a saturated sodium bicarbonate aqueous solution, separating liquid, extracting toluene, concentrating, and performing column chromatography separation to finally obtain a product 162mg, wherein the yield is as follows: 85 percent. Product characterization data were as follows: 1H NMR (500MHz, CDCl3) delta 7.27-7.18 (m, 5H), 5.38 (s, 1H), 4.08-3.96 (m, 1H), 2.94 (t, J =7.7Hz, 2H), 2.40 (t, J =7.7Hz, 2H), 1.06 (d, J =6.6Hz, 6H). 13C NMR (125MHz, CDCl3) delta 171.18,140.95,128.46,128.38,126.18,41.22,38.70,31.86,22.69.
Example 4: nickel-catalyzed C-alkylation of benzyl alcohol with N-cyclohexylacetamide:
Under an inert atmosphere, II (54mg, 15mol%) was added to the reaction tube, and the reaction tube was transferred to a glove box, followed by addition of potassium tert-amylate (379mg, 3mmol), starting benzyl alcohol (104. Mu.L, 1 mmol), substrate N-cyclohexylacetamide (423mg, 3mmol) and toluene (2 mL), and the reaction tube was sealed and transferred to the glove box. Reacting for 24 hours in an oil bath at 150 ℃, after the reaction is finished, adding 5mL of toluene to fully dissolve a reaction solution when a reaction system is cooled to room temperature, adjusting the pH to about 8-9 by using a saturated sodium bicarbonate aqueous solution, separating liquid, extracting toluene, concentrating, and performing column chromatography separation to finally obtain 185mg of a product, wherein the yield is as follows: 80 percent. Product characterization data are as follows: 1H NMR (400MHz, CDCl3) delta 7.41-7.09 (m, 5H), 5.39 (s, 1H), 3.79-3.71 (m, 1H), 2.96 (t, J =7.7Hz, 2H), 2.48-2.40 (m, 2H), 1.91-1.53 (m, 5H), 1.41-0.96 (m, 5H). 13C NMR (101MHz, CDCl3) delta 171.15,140.94,128.49,128.41,126.20,48.07,38.77,33.09,31.92,31.20,25.51,24.83,24.23.
Example 5: nickel-catalyzed C-alkylation of benzyl alcohol with 2-piperidone:
Under an inert atmosphere, II (54mg, 15mol%) was added to the reaction tube, and the reaction tube was transferred to a glove box, and potassium tert-amylate (379mg, 3mmol), starting benzyl alcohol (104. Mu.L, 1 mmol), substrate 2-piperidone (297mg, 3mmol) and toluene (2 mL) were sequentially added, and the reaction tube was sealed and transferred to the glove box. Reacting for 24 hours in an oil bath at 150 ℃, after the reaction is finished, adding 5mL of toluene to fully dissolve a reaction solution when a reaction system is cooled to room temperature, adjusting the pH to about 8-9 by using a saturated sodium bicarbonate aqueous solution, separating liquid, extracting toluene, concentrating, and performing column chromatography separation to finally obtain 149mg of a product, wherein the yield is as follows: 79 percent. Product characterization data were as follows: 1H NMR (500MHz, CDCl3) delta 7.31-7.27 (m, 2H), 7.23-7.18 (m, 3H), 6.57 (s, 1H), 3.42-3.39 (m, 1H), 3.34-3.22 (m, 2H), 2.69-2.65 (m, 1H), 2.59-2.52 (m, 1H), 1.85-1.60 (m, 3H), 1.46-1.44 (m, 1H). 13C NMR (126MHz, CDCl3) delta 165.68,142.23,135.48,129.42,128.75,127.72,117.81,42.29,41.06,15.07, 13.21).
Example 6: nickel-catalyzed C-alkylation of benzyl alcohol with indolone:
Under an inert atmosphere, II (54mg, 15mol%) was added to the reaction tube, and the reaction tube was transferred to a glove box, and potassium tert-amylate (379mg, 3mmol), starting benzyl alcohol (104. Mu.L, 1 mmol), substrate indolone (399mg, 3mmol) and toluene (2 mL) were sequentially added, and the reaction tube was sealed and transferred to the glove box. Reacting for 24 hours in an oil bath at 150 ℃, after the reaction is finished, adding 5mL of toluene to fully dissolve a reaction solution when a reaction system is cooled to room temperature, adjusting the pH to about 8-9 by using a saturated sodium bicarbonate aqueous solution, separating liquid, extracting toluene, concentrating, and performing column chromatography separation to finally obtain a product 181mg, wherein the yield is as follows: 81 percent. Product characterization data were as follows: 1H NMR (500MHz, CDCl3) delta 9.21 (s, 1H), 7.32-7.27 (m, 6H), 7.25-7.19 (m, 2H), 6.96-6.91 (m, 1H), 6.79 (d, J =7.4Hz, 1H), 3.82-3.79 (m, 1H), 3.57-3.53 (m, 1H), 3.01-2.98 (m, 1H), 13C NMR (MHz, CDCl3) delta 179.95,141.56,137.84,129.44,129.03,128.35,127.98,126.68,124.82,122.01,109.82,47.61,36.65.
Example 7: nickel-catalyzed C-alkylation of benzyl alcohol with N, N-diethylacetamide:
Under an inert atmosphere, II (54mg, 15mol%) was charged into a reaction tube, and the reaction tube was transferred into a glove box, and potassium tert-amylate (316 mg, 2.5mmol), raw benzyl alcohol (104. Mu.L, 1 mmol), substrate N, N-diethylacetamide (347mg, 3mmol) and toluene (2 mL) were sequentially added, and the reaction tube was sealed and transferred out of the glove box. Reacting for 24 hours in an oil bath at 150 ℃, after the reaction is finished, adding 5mL of toluene to fully dissolve a reaction solution when a reaction system is cooled to room temperature, adjusting the pH to about 8-9 by using a saturated sodium bicarbonate aqueous solution, separating liquid, extracting toluene, concentrating, and performing column chromatography separation to finally obtain 185mg of a product, wherein the yield is as follows: and 90 percent. Product characterization data were as follows: 1H NMR (500MHz, CDCl3) delta 7.28-7.16 (m, 5H), 3.38-3.36 (m, 2H), 3.22-3.20 (m, 2H), 3.01-2.94 (m, 2H), 2.63-2.52 (m, 2H), 1.11-1.07 (m, 6H), 13C NMR (125MHz, CDCl3) delta 171.24,141.57,128.45,128.43,126.05,41.89,40.20,35.07,31.66,14.27,13.08.
Example 8: the nickel catalyzes the C-alkylation reaction of the benzyl alcohol and the 1-acetylpiperidine:
Under an inert atmosphere, II (54mg, 15mol%) was charged into a reaction tube, and the reaction tube was transferred into a glove box, and potassium tert-amylate (316mg, 2.5mmol), starting benzyl alcohol (104. Mu.L, 1 mmol), substrate 1-acetylpiperidine (382mg, 3mmol) and toluene (2 mL) were sequentially added, and the reaction tube was sealed and transferred out of the glove box. Reacting for 24 hours in an oil bath at 150 ℃, after the reaction is finished, adding 5mL of toluene to fully dissolve a reaction solution when a reaction system is cooled to room temperature, adjusting the pH to about 8-9 by using a saturated sodium bicarbonate aqueous solution, separating liquid, extracting toluene, concentrating, and performing column chromatography separation to finally obtain 206mg of a product, wherein the yield is as follows: 95 percent. Product characterization data are as follows: 1H NMR (500mhz, cdcl3) δ 7.27-7.16 (m, 5H), 3.54 (t, J =5.0hz, 2h), 3.31 (t, J =5.0hz, 2h), 2.95 (t, J =10.0hz, 2h), 2.60 (t, J =10.0hz, 2h), 1.64-1.40 (m, 6H). 13C NMR (125mhz, cdcl3) δ 170.37,141.50,128.45,128.43,126.07,46.59,42.69,35.15,31.62,26.38,25.55,24.53.
Example 9: the nickel catalyzes the C-alkylation reaction of the benzyl alcohol and the 1-morpholine-1-ethanone:
Under an inert atmosphere, II (54mg, 15mol%) was added to the reaction tube, and the reaction tube was transferred to a glove box, and potassium tert-amylate (316mg, 2.5mmol), raw material benzyl alcohol (104. Mu.L, 1 mmol), substrate 1-morpholine-1-ethanone (384mg, 3mmol) and toluene (2 mL) were sequentially added thereto, and the reaction tube was sealed and transferred to a glove box. Reacting for 24 hours in an oil bath at 150 ℃, after the reaction is finished, adding 5mL of toluene to fully dissolve a reaction solution when a reaction system is cooled to room temperature, adjusting the pH to about 8-9 by using a saturated sodium bicarbonate aqueous solution, separating liquid, extracting toluene, concentrating, and performing column chromatography separation to finally obtain a product 191mg, wherein the yield is as follows: 87 percent. Product characterization data were as follows: 1H NMR (500MHz, CDCl3) delta 7.31-7.19 (m, 5H), 3.65-3.60 (m, 4H), 3.48 (t, J =5.0Hz, 2H), 3.33 (t, J =5.0Hz, 2H), 2.96 (t, J =10.0Hz, 2H), 2.59 (t, J =10.0Hz, 2H), 13C NMR (125MHz, CDCl3) delta 170.87,141.06,128.53,128.45,126.26,66.83,66.45,45.98,41.95,34.76,31.48.
Example 10: nickel catalysis of the C-alkylation reaction of benzyl alcohol with N, N-diethylphenylacetamide:
Under an inert atmosphere, II (54mg, 15mol%) was charged into a reaction tube, and the reaction tube was transferred into a glove box, and potassium tert-amylate (316mg, 2.5mmol), raw benzyl alcohol (104. Mu.L, 1 mmol), substrate N, N-diethylphenylacetamide (574mg, 3mmol) and toluene (2 mL) were sequentially added, and the reaction tube was sealed and transferred out of the glove box. Reacting for 24 hours in an oil bath at 150 ℃, after the reaction is finished, adding 5mL of toluene to fully dissolve a reaction solution when a reaction system is cooled to room temperature, adjusting the pH to about 8-9 by using a saturated sodium bicarbonate aqueous solution, separating liquid, extracting toluene, concentrating, and performing column chromatography separation to finally obtain a product 233mg, wherein the yield is as follows: 83 percent. Product characterization data were as follows: 1H NMR (500MHz, CDCl3) delta 7.30-7.10 (m, 10H), 3.93-3.30 (m, 1H), 3.53-3.50 (m, 1H), 3.40-3.19 (m, 3H), 3.07-2.89 (m, 2H), 1.03 (t, J =7.1Hz, 3H), 0.85 (t, J =7.1Hz, 3H), 13C NMR (125MHz, CDCl3) delta 171.55,140.21,140.19,129.23, 128.60,128.12,127.98,126.90,126.06,51.22,41.76,41.67,40.42,14.26,12.83.
Example 11: the nickel catalyzes the C-alkylation reaction of the benzyl alcohol and the 1-morpholine-2-phenyl ethyl ketone:
Under an inert atmosphere, II (54mg, 15mol%) was added to a reaction tube, and the reaction tube was transferred to a glove box, potassium tert-amylate (316mg, 2.5mmol), starting benzyl alcohol (104. Mu.L, 1 mmol), substrate 1-morpholine-2-phenylethanone (616mg, 3mmol), and toluene (2 mL) were sequentially added, and the reaction tube was sealed and transferred to the glove box. Reacting for 24 hours in an oil bath at 150 ℃, after the reaction is finished, adding 5mL of toluene to fully dissolve a reaction solution when a reaction system is cooled to room temperature, adjusting the pH to about 8-9 by using a saturated sodium bicarbonate aqueous solution, separating liquid, extracting toluene, concentrating, and performing column chromatography separation to finally obtain a product 263mg, wherein the yield is as follows: 89 percent. Product characterization data were as follows: 1H NMR (500MHz, CDCl3) delta 7.32-7.27 (m, 2H), 7.25-7.15 (m, 6H), 7.11-7.07 (m, 2H), 3.97-3.93 (m, 1H), 3.71-3.60 (m, 1H), 3.56-3.46 (m, 4H), 3.36-3.21 (m, 3H), 3.08-3.04 (m, 1H), 2.97-2.95 (m, 1H), 13C NMR (MHz 125, CDCl3) delta 171.15,139.81,139.53,129.22,128.80,128.24,127.88,127.16,126.23,66.72,66.23,50.82,46.13,42.49,40.99.
Example 12: nickel-catalyzed C-alkylation of benzyl alcohol with N-methylcaprolactam:
Under an inert atmosphere, II (54mg, 15mol%) was charged into a reaction tube, and the reaction tube was transferred into a glove box, and potassium tert-amylate (316mg, 2.5mmol), starting benzyl alcohol (104. Mu.L, 1 mmol), substrate N-methylcaprolactam (382mg, 3mmol) and toluene (2 mL) were sequentially added, and the reaction tube was sealed and transferred out of the glove box. Reacting for 24 hours in an oil bath at 150 ℃, after the reaction is finished, adding 5mL of toluene to fully dissolve a reaction solution when a reaction system is cooled to room temperature, adjusting the pH to about 8-9 by using a saturated sodium bicarbonate aqueous solution, separating liquid, extracting toluene, concentrating, and performing column chromatography separation to finally obtain 178mg of a product, wherein the yield is as follows: 82 percent. Product characterization data were as follows: 1H NMR (500MHz, CDCl3) delta 7.27-7.14 (m, 5H), 3.62-3.59 (m, 1H), 3.24-3.22 (m, 1H), 3.13-3.30 (m, 1H), 2.98 (s, 3H), 2.85-2.77 (m, 1H), 2.58-2.53 (m, 1H), 1.91-1.79 (m, 1H), 1.70-1.88 (m, 2H), 1.52-1.24 (m, 3H), 13C NMR (125MHz, CDCl3) delta 176.57,140.97,129.30,128.23,125.85,50.40,45.31,38.21,35.82,29.23,29.04,26.87.
Example 13: nickel-catalyzed C-alkylation of benzyl alcohol with 1-phenyl-2-pyrrolidone:
Under an inert atmosphere, II (54mg, 15mol%) was added to the reaction tube, and the reaction tube was transferred to a glove box, and potassium tert-amylate (316mg, 2.5mmol), raw material benzyl alcohol (104. Mu.L, 1 mmol), substrate 1-phenyl-2-pyrrolidone (484mg, 3mmol) and toluene (2 mL) were added in this order, and the reaction tube was sealed and transferred to the glove box. Reacting for 24 hours in an oil bath at 150 ℃, after the reaction is finished, adding 5mL of toluene to fully dissolve a reaction solution when a reaction system is cooled to room temperature, adjusting the pH to about 8-9 by using a saturated sodium bicarbonate aqueous solution, separating liquid, extracting toluene, concentrating, and performing column chromatography separation to finally obtain 221mg of a product, wherein the yield is as follows: 88 percent. Product characterization data are as follows: 1H NMR (500mhz, cdcl3) δ 7.65 (d, J =10hz, 2h), 7.39 (t, J =8.7, 2h), 7.33 (t, J =7.4hz, 2h), 7.30-7.26 (m, 3H), 7.18 (t, J =7.4hz, 1h), 3.78-3.69 (m, 1H), 3.65-3.60 (m, 1H), 3.36-3.32 (m, 1H), 2.95-2.85 (m, 1H), 2.85-2.83 (m, 1H), 2.25-2.14 (m, 1H), 1.93-1.80 (m, 1H), 13C NMR (125mhz, cdcl3) δ 175.13,139.54,139.26,129.08,128.82,128.52,126.42, 119.42, 49.45, 23.45, 37.17, 37.17.17, 14.17.17, 14.
Example 14: nickel-catalyzed C-alkylation of benzyl alcohol with 1-benzyl-2-pyrrolidone:
Under an inert atmosphere, II (54mg, 15mol%) was added to the reaction tube, and the reaction tube was transferred to a glove box, and potassium tert-amylate (316mg, 2.5mmol), starting benzyl alcohol (104. Mu.L, 1 mmol), substrate 1-benzyl-2-pyrrolidone (526mg, 3mmol) and toluene (2 mL) were sequentially added, and the reaction tube was sealed and transferred to the glove box. Reacting for 24 hours in an oil bath at 150 ℃, after the reaction is finished, adding 5mL of toluene to fully dissolve a reaction solution when a reaction system is cooled to room temperature, adjusting the pH to about 8-9 by using a saturated sodium bicarbonate aqueous solution, separating liquid, extracting toluene, concentrating, and performing column chromatography separation to finally obtain a product 228mg, wherein the yield is as follows: 86 percent. Product characterization data were as follows: 1H NMR (500MHz, CDCl3) delta 7.34-7.18 (m, 10H), 4.49-4.41 (m, 2H), 3.27-3.24 (m, 1H), 3.11-3.08 (m, 2H), 3.04-3.02 (m, 2H), 2.85-2.68 (m, 1H), 2.08-1.89 (m, 1H), 1.74-1.66 (m, 1H), 13C NMR (125MHz, CDCl3) delta 175.81,139.42,136.54,129.15,128.70,128.46,128.15,127.58,126.35,46.79,44.77,43.63,37.01,23.99.
Example 15: nickel-catalyzed C-alkylation of benzyl alcohol with 1-cyclohexyl-2-pyrrolidone:
Under an inert atmosphere, II (54mg, 15mol%) was charged into a reaction tube, and the reaction tube was transferred into a glove box, and potassium tert-amylate (316mg, 2.5mmol), raw material benzyl alcohol (104. Mu.L, 1 mmol), substrate 1-cyclohexyl-2-pyrrolidone (501mg, 3mmol) and toluene (2 mL) were sequentially added, and the reaction tube was sealed and transferred out of the glove box. Reacting for 24 hours in an oil bath at 150 ℃, after the reaction is finished, adding 5mL of toluene to fully dissolve a reaction solution when a reaction system is cooled to room temperature, adjusting the pH to about 8-9 by using a saturated sodium bicarbonate aqueous solution, separating liquid, extracting toluene, concentrating, and performing column chromatography separation to finally obtain a product 207mg, wherein the yield is as follows: 81 percent. Product characterization data are as follows: 1H NMR (500MHz, CDCl3) delta 7.30-7.19 (m, 5H), 3.96-3.90 (m, 1H), 3.21-3.05 (m, 3H), 2.75-2.62 (m, 2H), 2.08-1.94 (m, 1H), 1.81-1.57 (m, 6H), 1.43-1.23 (m, 4H), 1.12-1.01 (m, 1H), 13C NMR (125MHz, CDCl3) delta 175.08,139.57,129.07,128.35,126.20,50.62,44.19,41.06,37.04,30.21,25.46,24.31.
Example 16: nickel-catalyzed C-alkylation of benzyl alcohol with N-methylindolone:
Under an inert atmosphere, II (54mg, 15mol%) was added to the reaction tube, and the reaction tube was transferred to a glove box, and potassium tert-amylate (316mg, 2.5mmol), starting benzyl alcohol (104. Mu.L, 1 mmol), substrate N-methylindolone (442mg, 3mmol) and toluene (2 mL) were sequentially added, and the reaction tube was sealed and transferred to a glove box. Reacting for 24 hours in an oil bath at 150 ℃, after the reaction is finished, adding 5mL of toluene to fully dissolve a reaction solution when a reaction system is cooled to room temperature, adjusting the pH to about 8-9 by using a saturated sodium bicarbonate aqueous solution, separating liquid, extracting toluene, concentrating, and performing column chromatography separation to finally obtain a product 215mg, wherein the yield is as follows: 88 percent. Product characterization data are as follows: 1H NMR (500MHz, CDCl3) delta 7.27-7.14 (m, 6H), 6.94-6.89 (m, 1H), 6.74 (d, J =8.4Hz, 2H), 3.72-3.69 (m, 1H), 3.52-3.48 (m, 1H), 3.15 (s, 3H), 2.91-2.86 (m, 1H), 13C NMR (125MHz, CDCl3) delta 177.03,144.22,137.97,129.40,128.40,128.28,127.95,126.61,124.52,122.04,107.90,47.05,36.84,26.10.
Claims (7)
1. A process for catalyzing the C-alkylation of an alcohol with an amide using a tridentate NNO-Ni complex, the process comprising:
under the protection of inert gas, mixing an alcohol compound (III), an amide compound (IV), alkali, a tridentate NNO-Ni complex (I) and a reaction solvent, reacting for 8-48 h at 110-150 ℃, and then carrying out post-treatment on reaction liquid to obtain a product alkylated amide (V);
the base is R 5 OM or bis (trimethylsilyl) amino potassium/sodium/lithium; at R 5 In OM, R 5 Is H or C1-C10 alkylA group; m is alkali metal Li, na or K;
the tridentate NNO-Ni complex (I) has the following structural formula:
in the formula (I), the compound is shown in the specification,
R 1 、R 2 、R 3 、R 4 each independently is H, C1-C30 alkyl or C6-C30 aryl;
x is F, cl, br, I, OAc, acac or OTf;
n＝0～2；
in the above method, the structural formulas of the raw material alcohol compound (III), the amide compound (IV) and the product alkylated amide (V) are as follows:
in the formulae (III), (IV), (V),
R 6 is H or C1-C30 alkyl, C3-C7 cycloalkyl, naphthyl, heteroaryl, phenyl or substituted phenyl, wherein the phenyl ring of the substituted phenyl is substituted by one or more substituents which are respectively and independently C1-C30 alkyl, C1-C30 alkoxy, phenyl, hydroxymethyl, halogen or halogenated methyl;
R 7 is H or phenyl;
R 8 is H, C1-C30 alkyl, C6-C30 aryl, or C1-C30 alkyl or C6-C30 aryl containing one or more heteroatoms selected from O, S or N;
R 9 、R 10 each independently is H, C1-C30 alkyl, C6-C30 aryl, or C1-C30 alkyl or C6-C30 aryl containing one or more heteroatoms selected from O, S or N;
or, R 8 、R 9 And the groups therebetween, together form a ring, with or without one or more heteroatoms independently selected from O, S, or N in the ring;
or, R 9 、R 10 And N therebetween, together form a ring with or without one or more heteroatoms independently selected from O, S or N in the ring.
2. The method for catalyzing the C-alkylation reaction of an alcohol with an amide using a tridentate NNO-Ni complex as claimed in claim 1, wherein the ratio of the amounts of the substance of the alcohol compound (III), the amide compound (IV), the base, the tridentate NNO-Ni complex (I) is 1:3 to 10:1.5 to 3.0:0.05 to 0.2.
3. The method for catalyzing the C-alkylation of an alcohol with an amide using a tridentate NNO-Ni complex as recited in claim 1, wherein the base is potassium tert-amylate.
4. The method for catalyzing the C-alkylation reaction of an alcohol with an amide using a tridentate NNO-Ni complex as set forth in claim 1, wherein the reaction solvent is one or a mixed solvent of two or more selected from the group consisting of toluene, tetrahydrofuran, anisole, cyclopentyl methyl ether, 1, 4-dioxane, n-heptane and dimethyl ether in any ratio.
5. The method for catalyzing the C-alkylation reaction of an alcohol with an amide using a tridentate NNO-Ni complex as claimed in claim 1, wherein the molar ratio of the reaction solvent to the alcohol ranges from 0 to 4:1mL/mmol.
6. The method for catalyzing the C-alkylation of an alcohol with an amide using a tridentate NNO-Ni complex as claimed in claim 1, wherein the post-treatment method is: after the reaction is finished, cooling the reaction liquid to room temperature, diluting the reaction liquid by toluene, adjusting the pH value to 8-9 by saturated sodium bicarbonate aqueous solution, separating liquid, extracting the water phase by toluene, combining organic phases, concentrating, separating by silica gel column chromatography, and performing separation by using a petroleum ether-ethyl acetate volume ratio of 10:1 as eluent, collecting the eluent containing the target compound, evaporating the solvent and drying to obtain the product alkylated amide (V).
7. The method of catalyzing a C-alkylation reaction of an alcohol with an amide using a tridentate NNO-Ni complex of claim 1, wherein the tridentate NNO-Ni complex has a structural formula as follows:
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| CN111187176A (en) * | 2020-01-23 | 2020-05-22 | 浙江工业大学 | Method for preparing N-vinyl amide compound under catalysis of copper salt |
| CN112961079A (en) * | 2021-03-04 | 2021-06-15 | 浙江工业大学 | Method for dehydrating primary amide into nitriles by cobalt catalysis |
| CN114031477A (en) * | 2021-11-02 | 2022-02-11 | 浙江工业大学 | Method for reducing amide compounds into amine compounds by cobalt catalysis |
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Patent Citations (3)
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|---|---|---|---|---|
| CN111187176A (en) * | 2020-01-23 | 2020-05-22 | 浙江工业大学 | Method for preparing N-vinyl amide compound under catalysis of copper salt |
| CN112961079A (en) * | 2021-03-04 | 2021-06-15 | 浙江工业大学 | Method for dehydrating primary amide into nitriles by cobalt catalysis |
| CN114031477A (en) * | 2021-11-02 | 2022-02-11 | 浙江工业大学 | Method for reducing amide compounds into amine compounds by cobalt catalysis |
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| MIDYA, S. P.;: "E. Ni-Catalyzed α-Alkylation of Unactivated Amides and Esters with Alcohols by Hydrogen Auto-Transfer Strategy.", 《CHEMSUSCHEM》, pages 3911 * |
| RUEPING, M. ETAL: "Sustainable Alkylation of Unactivated Esters and Amides with Alcohols Enabled by Manganese Catalysis", 《ORG. LETT.》, pages 7779 * |
| 宗志建: "基于四氢喹啉骨架开发氮配体及其钴配合 物的催化反应研究", 《浙江工业大学博士学位论》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN116496324A (en) * | 2023-04-26 | 2023-07-28 | 河北师范大学 | Ruthenium complex, preparation method thereof and application thereof in alkylation reaction of indole and alcohol |
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