CN112175006A - A kind of preparation method of pyridinediphenylphosphine derivative - Google Patents
A kind of preparation method of pyridinediphenylphosphine derivative Download PDFInfo
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- CN112175006A CN112175006A CN202011243908.7A CN202011243908A CN112175006A CN 112175006 A CN112175006 A CN 112175006A CN 202011243908 A CN202011243908 A CN 202011243908A CN 112175006 A CN112175006 A CN 112175006A
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- pyridine
- diphenylphosphine
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- dibromopyridine
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- 238000002360 preparation method Methods 0.000 title abstract description 12
- 238000006243 chemical reaction Methods 0.000 claims abstract description 40
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 20
- GPAYUJZHTULNBE-UHFFFAOYSA-N diphenylphosphine Chemical compound C=1C=CC=CC=1PC1=CC=CC=C1 GPAYUJZHTULNBE-UHFFFAOYSA-N 0.000 claims abstract description 16
- 238000000034 method Methods 0.000 claims abstract description 15
- OXGVFLHWGRTWCA-UHFFFAOYSA-N diphenylphosphane;pyridine Chemical class C1=CC=NC=C1.C=1C=CC=CC=1PC1=CC=CC=C1 OXGVFLHWGRTWCA-UHFFFAOYSA-N 0.000 claims abstract description 12
- 239000002904 solvent Substances 0.000 claims abstract description 11
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 10
- 150000003222 pyridines Chemical class 0.000 claims abstract description 9
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims abstract description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 9
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 6
- 239000000126 substance Substances 0.000 claims description 6
- FEYDZHNIIMENOB-UHFFFAOYSA-N 2,6-dibromopyridine Chemical compound BrC1=CC=CC(Br)=N1 FEYDZHNIIMENOB-UHFFFAOYSA-N 0.000 claims description 5
- UYZOWFBHUSJQPJ-UHFFFAOYSA-N 2,6-dibromo-4-(trifluoromethyl)pyridine Chemical compound FC(F)(F)C1=CC(Br)=NC(Br)=C1 UYZOWFBHUSJQPJ-UHFFFAOYSA-N 0.000 claims description 2
- VMKXRAUUPMNAOQ-UHFFFAOYSA-N 2,6-dibromo-4-fluoropyridine Chemical compound BrC1=NC(=CC(=C1)F)Br VMKXRAUUPMNAOQ-UHFFFAOYSA-N 0.000 claims description 2
- FBLLPCQLOGKHAL-UHFFFAOYSA-N 2,6-dibromo-4-methoxypyridine Chemical compound COC1=CC(Br)=NC(Br)=C1 FBLLPCQLOGKHAL-UHFFFAOYSA-N 0.000 claims description 2
- LMFFGAUQSWOBOS-UHFFFAOYSA-N 2,6-dibromo-4-phenylpyridine Chemical compound BrC1=NC(Br)=CC(C=2C=CC=CC=2)=C1 LMFFGAUQSWOBOS-UHFFFAOYSA-N 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 2
- IMRWILPUOVGIMU-CDYZYAPPSA-N 2-bromopyridine Chemical group BrC1=CC=CC=[15N]1 IMRWILPUOVGIMU-CDYZYAPPSA-N 0.000 claims 1
- OCRVOIYJNKSVEG-UHFFFAOYSA-N C1=CC(=C(N=C1)Br)CF Chemical compound C1=CC(=C(N=C1)Br)CF OCRVOIYJNKSVEG-UHFFFAOYSA-N 0.000 claims 1
- 239000007983 Tris buffer Substances 0.000 claims 1
- 239000007810 chemical reaction solvent Substances 0.000 claims 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 1
- 238000003786 synthesis reaction Methods 0.000 abstract description 9
- 239000003054 catalyst Substances 0.000 abstract description 7
- 238000011031 large-scale manufacturing process Methods 0.000 abstract 1
- 239000010970 precious metal Substances 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
- 239000000047 product Substances 0.000 description 17
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 12
- 238000004440 column chromatography Methods 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 8
- 239000003480 eluent Substances 0.000 description 8
- 238000004809 thin layer chromatography Methods 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 239000012043 crude product Substances 0.000 description 7
- 239000012074 organic phase Substances 0.000 description 7
- 238000002390 rotary evaporation Methods 0.000 description 7
- -1 catalysis Substances 0.000 description 5
- IMRWILPUOVGIMU-UHFFFAOYSA-N 2-bromopyridine Chemical compound BrC1=CC=CC=N1 IMRWILPUOVGIMU-UHFFFAOYSA-N 0.000 description 4
- QKJAZPHKNWSXDF-UHFFFAOYSA-N 2-bromoquinoline Chemical compound C1=CC=CC2=NC(Br)=CC=C21 QKJAZPHKNWSXDF-UHFFFAOYSA-N 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- 229910052723 transition metal Inorganic materials 0.000 description 3
- 150000003624 transition metals Chemical class 0.000 description 3
- AWBDARKONATUHX-UHFFFAOYSA-N 2-bromo-4-methoxypyridine Chemical compound COC1=CC=NC(Br)=C1 AWBDARKONATUHX-UHFFFAOYSA-N 0.000 description 2
- ZIDIKYIZXMYHAW-UHFFFAOYSA-N 2-bromo-6-fluoropyridine Chemical compound FC1=CC=CC(Br)=N1 ZIDIKYIZXMYHAW-UHFFFAOYSA-N 0.000 description 2
- XIYPPJVLAAXYAB-UHFFFAOYSA-N 2-bromo-6-phenylpyridine Chemical compound BrC1=CC=CC(C=2C=CC=CC=2)=N1 XIYPPJVLAAXYAB-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- UHOVQNZJYSORNB-MZWXYZOWSA-N benzene-d6 Chemical compound [2H]C1=C([2H])C([2H])=C([2H])C([2H])=C1[2H] UHOVQNZJYSORNB-MZWXYZOWSA-N 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 238000009776 industrial production Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- NHKJPPKXDNZFBJ-UHFFFAOYSA-N phenyllithium Chemical compound [Li]C1=CC=CC=C1 NHKJPPKXDNZFBJ-UHFFFAOYSA-N 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- BMYQNHCCMHXCBE-UHFFFAOYSA-N (4-methoxypyridin-2-yl)-diphenylphosphane Chemical compound COC1=CC=NC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 BMYQNHCCMHXCBE-UHFFFAOYSA-N 0.000 description 1
- PKLZMHUUPARTDZ-UHFFFAOYSA-N (4-methylpyridin-2-yl)-diphenylphosphane Chemical compound CC1=CC=NC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 PKLZMHUUPARTDZ-UHFFFAOYSA-N 0.000 description 1
- UNCDYUGALDQNLL-UHFFFAOYSA-N (6-diphenylphosphanylpyridin-2-yl)-diphenylphosphane Chemical compound C1=CC=CC=C1P(C=1N=C(C=CC=1)P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 UNCDYUGALDQNLL-UHFFFAOYSA-N 0.000 description 1
- WJOVTBUNFQDWRK-UHFFFAOYSA-N (6-fluoropyridin-2-yl)-diphenylphosphane Chemical compound FC1=CC=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=N1 WJOVTBUNFQDWRK-UHFFFAOYSA-N 0.000 description 1
- OHBIPNNTWKNAGC-UHFFFAOYSA-N 2,6-dibromo-4-methylpyridine Chemical compound CC1=CC(Br)=NC(Br)=C1 OHBIPNNTWKNAGC-UHFFFAOYSA-N 0.000 description 1
- LSZMVESSGLHDJE-UHFFFAOYSA-N 2-bromo-4-methylpyridine Chemical compound CC1=CC=NC(Br)=C1 LSZMVESSGLHDJE-UHFFFAOYSA-N 0.000 description 1
- DNWSVXHWEWBVSJ-UHFFFAOYSA-N 2-diphenylphosphorylpyridine Chemical compound C=1C=CC=CC=1P(C=1N=CC=CC=1)(=O)C1=CC=CC=C1 DNWSVXHWEWBVSJ-UHFFFAOYSA-N 0.000 description 1
- 238000007259 addition reaction Methods 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- XZWFALQAPDAOON-UHFFFAOYSA-N diphenyl(quinolin-2-yl)phosphane Chemical compound C1=CC=CC=C1P(C=1N=C2C=CC=CC2=CC=1)C1=CC=CC=C1 XZWFALQAPDAOON-UHFFFAOYSA-N 0.000 description 1
- HTFATWMNNPRCRJ-UHFFFAOYSA-N diphenyl-(6-phenylpyridin-2-yl)phosphane Chemical compound C1=CC=CC=C1P(C=1N=C(C=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 HTFATWMNNPRCRJ-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 239000013110 organic ligand Substances 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- NBRKLOOSMBRFMH-UHFFFAOYSA-N tert-butyl chloride Chemical compound CC(C)(C)Cl NBRKLOOSMBRFMH-UHFFFAOYSA-N 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/576—Six-membered rings
- C07F9/58—Pyridine rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/576—Six-membered rings
- C07F9/60—Quinoline or hydrogenated quinoline ring systems
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Pyridine Compounds (AREA)
Abstract
本发明涉及一种吡啶二苯基膦衍生物的制备方法，属有机合成领域。该方法在氮气保护下，将吡啶衍生物、二苯基膦、KOH加入溶剂中，100～120℃下反应，获得吡啶二苯基膦衍生物。本发明以KOH为催化剂，避免使用贵金属催化剂，降低了成本，绿色环保；而且操作安全稳定，产率高，适合规模化生产。The invention relates to a preparation method of a pyridine diphenylphosphine derivative, belonging to the field of organic synthesis. In the method, under nitrogen protection, pyridine derivatives, diphenylphosphine and KOH are added to a solvent, and the reaction is carried out at 100-120° C. to obtain pyridine diphenylphosphine derivatives. The invention uses KOH as the catalyst, avoids the use of precious metal catalysts, reduces the cost, and is green and environmentally friendly; and the operation is safe and stable, the yield is high, and it is suitable for large-scale production.
Description
Technical Field
The invention belongs to the technical field of preparation of organic compounds, relates to a preparation method of a diphenylphosphine derivative, and particularly relates to a preparation method of a pyridine diphenylphosphine derivative.
Background
The pyridine diphenylphosphine derivative is an important chemical intermediate material and a catalyst ligand, and is widely applied to the fields of medicines, pesticides, catalysis, materials and the like. The synthesis methods of pyridine diphenylphosphine derivatives reported at home and abroad at present are generally divided into the following three types:
the first method is to use pyridine metal reagent to react with diphenyl phosphine halide. The method uses an organic metal reagent which is sensitive to water and oxygen and has very high activity, the reaction condition is harsh, the compatibility of functional groups is poor, quantitative metal salt byproducts are generated, and the method does not meet the development requirement of green chemistry (Chin. J. org. chem., 2018, 38(8), 2151-ion 2160).
The second method is to use alkali metal to react with organophosphorus reagent to generate diphenylphosphine alkali metal salt, and then react with halogenated pyridine compound to prepare the product. The method also needs very harsh operating conditions, if triphenylphosphine is used as a starting raw material, phenyl lithium as an impurity is easy to generate, the activity of the method is high, the subsequent reaction is influenced, the phenyl lithium generated in the reaction process is consumed by adding chloro-tert-butane, and the method is not easy to operate industrially; while the use of diphenylphosphine and butyllithium as starting materials requires very low temperatures and strict anhydrous and oxygen-free environments (chem. Eur. J., 2009, 15(29), 7167-.
A third method is the preparation of halogenated aromatics by transition metal catalyzed synthesis with diphenylphosphine, which uses expensive transition metal catalysts, or transition metal complex catalysts that are difficult to obtain, which increase the cost and difficulty of the reaction and are not suitable for industrial operation (chem. Commun., 2015, 51(35), 7540-7542; J. organomet. chem., 2018, 866, 50-58). Therefore, the improvement of the preparation method of the pyridine diphenylphosphine is urgently needed to meet the requirement of industrial production.
Disclosure of Invention
The invention aims to provide a preparation method of pyridine diphenyl phosphine derivatives, which has the advantages of mild reaction conditions, wide application range, high yield, low cost and accordance with green chemical requirements.
In order to realize the purpose of the invention, the following technical scheme is adopted:
the method for preparing the pyridine diphenyl phosphine derivative comprises the following steps: adding a pyridine derivative, diphenylphosphine and KOH into a solvent, and reacting at 100-120 ℃ under the protection of nitrogen to obtain the pyridine diphenylphosphine derivative; the molar ratio of the pyridine derivative to the diphenylphosphine to the KOH is 1 to (1-2) to (3-5).
The pyridine derivative is shown as the following chemical structural general formula:
wherein R is selected from H, F, methyl, methoxy, CF3Phenyl, etc.;
the chemical structural general formula of the pyridine diphenylphosphine derivative is shown as follows:
in a preferred embodiment, the pyridine derivative is selected from the group consisting of 2-bromopyridine, 3 (or 4 or 5 or 6) -fluoro-2-bromopyridine, 3 (or 4 or 5 or 6) -methyl-2-bromopyridine, 3 (or 4 or 5 or 6) -methoxy-2-bromopyridine, 3 (or 4 or 5 or 6) -trifluoromethyl-2-bromopyridine, 3 (or 4 or 5 or 6) -phenyl-2-bromopyridine, 2, 6-dibromopyridine, 4-fluoro-2, 6-dibromopyridine, 4-methyl-2, 6-dibromopyridine, 4-methoxy-2, 6-dibromopyridine, 4-trifluoromethyl-2, 6-dibromopyridine, 4-phenyl-2, 6-dibromopyridine.
In the technical scheme, the reaction is tracked by using thin layer chromatography until the reaction is completely finished.
In a preferred technical scheme, the solvent is DMF or DMSO.
In a preferred technical scheme, the reaction temperature is 100-110 ℃.
In the preferred technical scheme, after the reaction is finished, the product is subjected to column chromatography separation and purification treatment; during column chromatography, dichloromethane is used as an eluent.
The reaction process of the above technical scheme can be expressed as follows:
due to the application of the technical scheme, compared with the prior art, the invention has the following advantages:
1. the method adopts KOH as the catalyst, is cheap and easy to obtain, does not need noble metal catalysts and other organic ligands, has high utilization rate of raw materials and high product yield of more than 90 percent, reduces the generation of wastes and greatly reduces the cost.
2. The preparation method disclosed by the invention has wide application range, and can be used for reacting 2-bromopyridine with substituents at 3, 4, 5 and 6 positions and 2, 6-dibromopyridine with substituents at 4 positions to introduce diphenyl phosphine groups into a pyridine ring. In addition, the preparation method is also suitable for polycyclic benzopyrines such as 2-bromoquinoline.
3. The preparation method disclosed by the invention is mild in reaction conditions, simple in reaction operation and post-treatment process, green, environment-friendly, high in safety and suitable for industrial production.
4. The possible mechanism of the invention is: under the catalytic action of KOH, one molecule of HBr is firstly removed from a pyridine ring to generate a high-activity intermediate pyridyne, and then an addition reaction is carried out to introduce a functional group to obtain a target compound.
Detailed Description
The invention is further described below with reference to the following examples:
the first embodiment is as follows: synthesis of 2-diphenylphosphinylpyridine
1.58g (10mmol) of 2-bromopyridine and 2.79g (15mmol) of diphenylphosphine were added to 20ml of oxygen-free DMF, followed by addition of KOH2.24g (40mmol) and reaction at 110 ℃ under nitrogen. And (5) tracking the reaction progress by thin-layer chromatography until the 2-bromopyridine completely reacts, and finishing the reaction. The reaction solution was extracted with ethyl acetate and water, the organic phase was removed by rotary evaporation to remove the solvent, and the crude product was separated by column chromatography (eluent dichloromethane) to give the desired product (93% yield). Analytical data for the product are as follows:1 H NMR (400 MHz , CDCl3)： 8.73 (d, J = 3.6 Hz, 1H), 7.55 (t, J = 7.6 Hz, 1H), 7.40-7.25 (m, 10H), 7.16 (t, J = 5.8 Hz, 1H), 7.09 (d, J = 8.0 Hz, 1H) ppm。
example two: synthesis of 2-diphenylphosphino-4-methylpyridine
2-bromo1.72g (10mmol) of-4-methylpyridine and 3.72g (20mmol) of diphenylphosphine were added to 20ml of oxygen-free DMF, followed by addition of KOH2.24g (40mmol) and reaction at 110 ℃ under nitrogen. And (5) tracking the reaction progress by thin-layer chromatography until the 2-bromo-4-methylpyridine completely reacts, and finishing the reaction. The reaction solution was extracted with ethyl acetate and water, the organic phase was removed by rotary evaporation to remove the solvent, and the crude product was separated by column chromatography (eluent dichloromethane) to give the desired product (91% yield). Analytical data for the product are as follows:1 H NMR (400 MHz , CDCl3)： 8.55 (d, J = 4.6 Hz, 1H), 7.42-7.26 (m, 10H), 7.03 (d, J = 4.1 Hz, 1H), 6.94 (s, 1H), 2.26 (s, 3H) ppm。
example three: synthesis of 2-diphenylphosphino-6-fluoropyridine
1.76g (10mmol) of 2-bromo-6-fluoropyridine and 2.79g (15mmol) of diphenylphosphine were added to 20ml of oxygen-free DMSO followed by KOH1.68g (30mmol) and reacted at 105 ℃ under nitrogen. And (5) tracking the reaction progress by thin-layer chromatography until the 2-bromo-6-fluoropyridine completely reacts, and finishing the reaction. The reaction solution was extracted with ethyl acetate and water, the organic phase was removed by rotary evaporation to remove the solvent, and the crude product was separated by column chromatography (eluent dichloromethane) to give the desired product (92% yield). Analytical data for the product are as follows:1 H NMR (400 MHz , CDCl3)： 7.67-7.59 (m, 1H), 7.45 -7.33 (m, 10H), 6.98 -6.93 (m, 1H), 6.81 -6.76 (m, 1H)ppm。
example four: synthesis of 2-diphenylphosphino-4-methoxypyridine
1.88g (10mmol) of 2-bromo-4-methoxypyridine and 1.86g (10mmol) of diphenylphosphine were added to 20ml of oxygen-free DMF, followed by addition of KOH1.68g (30mmol), and reacted at 110 ℃ under nitrogen. And (5) tracking the reaction progress by thin-layer chromatography until the 2-bromo-4-methoxypyridine completely reacts, and finishing the reaction. The reaction solution was extracted with ethyl acetate and water, the organic phase was removed by rotary evaporation to remove the solvent, and the crude product was separated by column chromatography (eluent dichloromethane) to give the desired product (93% yield). Analytical data for the product are as follows:1 H NMR (400 MHz, CDCl3)： 8.50-8.47 (m, 1H), 7.42-7.33 (m, 10H), 6.73-6.70 (m, 1H), 6.66-6.63 (m, 1H), 3.72 (s, 3H) ppm。
example five: synthesis of 2-diphenylphosphino-6-phenylpyridine
2.34g (10mmol) of 2-bromo-6-phenylpyridine and 2.79g (15mmol) of diphenylphosphine were added to 20ml of oxygen-free DMF, followed by addition of KOH2.24g (40mmol), and reacted at 100 ℃ under nitrogen. And (5) tracking the reaction progress by thin-layer chromatography until the 2-bromo-6-phenylpyridine completely reacts, and finishing the reaction. The reaction solution was extracted with ethyl acetate and water, the organic phase was removed by rotary evaporation to remove the solvent, and the crude product was separated by column chromatography (eluent dichloromethane) to give the desired product (90% yield). Analytical data for the product are as follows:1 H NMR (400 MHz, C6D6)： 8.03-7.99 (m, 2H), 7.59-7.51 (m, 4H), 7.21-7.04 (m, 10H), 7.00-6.96 (m, 2H) ppm。
example six: synthesis of 2, 6-di (diphenylphosphino) pyridine
2.08g (10mmol) of 2, 6-dibromopyridine and 3.72g (20mmol) of diphenylphosphine were added to 20ml of oxygen-free DMF, followed by addition of KOH2.24g (40mmol) and reaction at 110 ℃ under nitrogen protection. And (5) tracking the reaction progress by thin-layer chromatography until the 2, 6-dibromopyridine is completely reacted and the reaction is finished. The reaction solution was extracted with ethyl acetate and water, the organic phase was removed by rotary evaporation to remove the solvent, and the crude product was separated by column chromatography (eluent dichloromethane) to give the desired product (91% yield). Analytical data for the product are as follows:1 H NMR (400 MHz , CDCl3)： 7.72 -7.68 (m, 1H), 7.48-7.41 (m, 14H), 7.11-7.20 (m, 8H)ppm。
example seven: synthesis of 2-diphenylphosphinoquinoline
2.08g (10mmol) of 2-bromoquinoline and 3.72g (20mmol) of diphenylphosphine were added to 20ml of oxygen-free DMF, followed by addition of KOH2.8g (50mmol) and reaction at 110 ℃ under nitrogen. And (5) tracking the reaction progress by thin-layer chromatography until the 2-bromoquinoline completely reacts, and finishing the reaction. The reaction solution was extracted with ethyl acetate and water, the organic phase was removed by rotary evaporation to remove the solvent, and the crude product was separated by column chromatography (eluent dichloromethane) to give the desired product (92% yield). Analytical data for the product are as follows:1 H NMR (400 MHz , CDCl3)： 8.11 (d, J = 8.8 Hz, 1H), 7.85 (d, J = 8.4 Hz, 1H), 7.62 (d, J = 8.4 Hz, 1H), 7.57 (t, J = 7.8 Hz, 1H), 7.52-7.40 (m, 4H), 7.38 (t, J = 7.6 Hz, 1H), 7.30-7.21 (m, 6H), 7.15 (d, J = 8.4 Hz, 1H)ppm。
Claims (3)
Priority Applications (1)
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| CN113980049A (en) * | 2021-11-19 | 2022-01-28 | 河南省科学院化学研究所有限公司 | Preparation method of diphenylphosphine substituted indole derivative |
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