CN111004282A - Preparation method of 4, 12-bis (diphenylphosphino) - [2.2] -p-cyclophane - Google Patents
Preparation method of 4, 12-bis (diphenylphosphino) - [2.2] -p-cyclophane Download PDFInfo
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- CN111004282A CN111004282A CN201911315543.1A CN201911315543A CN111004282A CN 111004282 A CN111004282 A CN 111004282A CN 201911315543 A CN201911315543 A CN 201911315543A CN 111004282 A CN111004282 A CN 111004282A
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- 238000002360 preparation method Methods 0.000 title claims abstract description 19
- -1 diphenylphosphino Chemical group 0.000 title claims abstract description 17
- 238000006243 chemical reaction Methods 0.000 claims abstract description 24
- 238000000034 method Methods 0.000 claims abstract description 11
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims abstract description 8
- 235000011114 ammonium hydroxide Nutrition 0.000 claims abstract description 8
- 238000005406 washing Methods 0.000 claims abstract description 8
- 239000003054 catalyst Substances 0.000 claims abstract description 7
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims abstract description 6
- 229910052802 copper Inorganic materials 0.000 claims abstract description 6
- 239000010949 copper Substances 0.000 claims abstract description 6
- 238000010438 heat treatment Methods 0.000 claims abstract description 6
- XGRJZXREYAXTGV-UHFFFAOYSA-N chlorodiphenylphosphine Chemical compound C=1C=CC=CC=1P(Cl)C1=CC=CC=C1 XGRJZXREYAXTGV-UHFFFAOYSA-N 0.000 claims abstract description 3
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 24
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 21
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims description 21
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 12
- 238000006722 reduction reaction Methods 0.000 claims description 9
- 238000010992 reflux Methods 0.000 claims description 9
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 8
- 238000002425 crystallisation Methods 0.000 claims description 7
- 230000008025 crystallization Effects 0.000 claims description 7
- 238000001035 drying Methods 0.000 claims description 7
- LVKCSZQWLOVUGB-UHFFFAOYSA-M magnesium;propane;bromide Chemical compound [Mg+2].[Br-].C[CH-]C LVKCSZQWLOVUGB-UHFFFAOYSA-M 0.000 claims description 7
- 238000010791 quenching Methods 0.000 claims description 7
- 230000000171 quenching effect Effects 0.000 claims description 7
- 238000003756 stirring Methods 0.000 claims description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- 229910021595 Copper(I) iodide Inorganic materials 0.000 claims description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 claims description 6
- ZDHXKXAHOVTTAH-UHFFFAOYSA-N trichlorosilane Chemical compound Cl[SiH](Cl)Cl ZDHXKXAHOVTTAH-UHFFFAOYSA-N 0.000 claims description 6
- 239000005052 trichlorosilane Substances 0.000 claims description 6
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 5
- 235000002906 tartaric acid Nutrition 0.000 claims description 5
- 239000011975 tartaric acid Substances 0.000 claims description 5
- 229910021591 Copper(I) chloride Inorganic materials 0.000 claims description 4
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 claims description 4
- 229940045803 cuprous chloride Drugs 0.000 claims description 4
- 239000003960 organic solvent Substances 0.000 claims description 4
- 229910021589 Copper(I) bromide Inorganic materials 0.000 claims description 3
- NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 claims description 3
- 239000007788 liquid Substances 0.000 claims description 3
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 claims description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 2
- 239000008096 xylene Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 1
- TWJZEWZJBZANTG-UHFFFAOYSA-M magnesium;propan-2-olate;bromide Chemical compound [Br-].CC(C)O[Mg+] TWJZEWZJBZANTG-UHFFFAOYSA-M 0.000 abstract description 5
- 238000009776 industrial production Methods 0.000 abstract description 4
- 239000000203 mixture Substances 0.000 abstract 1
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 12
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 10
- 238000005160 1H NMR spectroscopy Methods 0.000 description 8
- QPQGTZMAQRXCJW-UHFFFAOYSA-N [chloro(phenyl)phosphoryl]benzene Chemical compound C=1C=CC=CC=1P(=O)(Cl)C1=CC=CC=C1 QPQGTZMAQRXCJW-UHFFFAOYSA-N 0.000 description 6
- 229910052786 argon Inorganic materials 0.000 description 6
- USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 239000003446 ligand Substances 0.000 description 5
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- 238000005481 NMR spectroscopy Methods 0.000 description 4
- 239000003638 chemical reducing agent Substances 0.000 description 4
- 229960001270 d- tartaric acid Drugs 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 4
- 230000005311 nuclear magnetism Effects 0.000 description 4
- 238000001228 spectrum Methods 0.000 description 4
- YFPJFKYCVYXDJK-UHFFFAOYSA-N Diphenylphosphine oxide Chemical compound C=1C=CC=CC=1[P+](=O)C1=CC=CC=C1 YFPJFKYCVYXDJK-UHFFFAOYSA-N 0.000 description 3
- 229960001367 tartaric acid Drugs 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- OTCKOJUMXQWKQG-UHFFFAOYSA-L magnesium bromide Chemical compound [Mg+2].[Br-].[Br-] OTCKOJUMXQWKQG-UHFFFAOYSA-L 0.000 description 2
- 229910001623 magnesium bromide Inorganic materials 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000004679 31P NMR spectroscopy Methods 0.000 description 1
- 238000009876 asymmetric hydrogenation reaction Methods 0.000 description 1
- 239000012018 catalyst precursor Substances 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- GPAYUJZHTULNBE-UHFFFAOYSA-N diphenylphosphine Chemical compound C=1C=CC=CC=1PC1=CC=CC=C1 GPAYUJZHTULNBE-UHFFFAOYSA-N 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000001307 helium Substances 0.000 description 1
- 229910052734 helium Inorganic materials 0.000 description 1
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 1
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
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- 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
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/50—Organo-phosphines
- C07F9/5022—Aromatic phosphines (P-C aromatic linkage)
-
- 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
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/50—Organo-phosphines
- C07F9/505—Preparation; Separation; Purification; Stabilisation
- C07F9/509—Preparation; Separation; Purification; Stabilisation by reduction of pentavalent phosphorus derivatives, e.g. -P=X with X = O, S, Se or -P-Hal2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
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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)
- Catalysts (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a preparation method of 4, 12-bis (diphenylphosphino) - [2.2] -p-cyclophane. The method comprises the following steps: adding magnesium isopropoxide bromide dropwise into a solution of o-dibromo- [2.2] p-cyclophane, adding a copper catalyst CuX and diphenylphosphine chloride, heating for reaction, washing, separating and crystallizing to obtain a mixture ammonia water, obtaining 4, 12-bis (diphenylphosphino) - [2.2] -p-cyclophane, and finally obtaining the chiral 4, 12-bis (diphenylphosphino) - [2.2] -p-cyclophane through resolution and reduction. Compared with the traditional process, the method has the advantages of obviously improving the reaction safety, greatly reducing the cost and being suitable for industrial production.
Description
Technical Field
The invention relates to the technical field of organic chemistry, in particular to the field of synthesis of chiral phosphine ligands, and particularly relates to a preparation method of 4, 12-bis (diphenylphosphino) - [2.2] -p-cyclophane.
Background
4, 12-bis (diphenyl oxide) - [2.2] -p-cyclophane is used as a chiral phosphine ligand and is also a precursor of a chiral rhodium catalyst, has wide application in the chemical industry field, and is a catalyst precursor of an important asymmetric hydrogenation reaction in the synthesis process.
The literature reports about a method for synthesizing 4, 12-bis (diphenyloxy) - [2.2] -p-cycloaralkyl, which mainly comprises the steps of reacting o-dibromo- [2.2] p-cycloaralkyl with tert-butyl lithium to form a lithium reagent, reacting with diphenylphosphonic chloride under the action of magnesium bromide ethyl ether to obtain 4, 12-bis (diphenylphosphinoxy) - [2.2] -p-cycloaralkyl, and then obtaining chiral 4, 12-bis (diphenyloxy) - [2.2] -p-cycloaralkyl through resolution and reduction (US 5874629). In addition, the reaction of o-dibromo- [2.2] p-cycloparaffin with n-butyllithium to form a lithium reagent (eur.j.org.chem.2013, 4523-4532) is reported, and both methods require the use of a butyl lithium reagent with high risk and a magnesium bromide ether reagent with high cost and poor stability, which are not suitable for industrial production. In view of the market application prospect of the chiral phosphine ligand in the field of asymmetric catalysis, the development of a 4, 12-bis (diphenyloxide) - [2.2] -p-cyclophane synthetic method with high efficiency, low cost and high safety is necessary.
Disclosure of Invention
The invention aims to provide a preparation method of 4, 12-bis (diphenyloxide) - [2.2] -p-cyclophane chiral phosphine ligand, which has high efficiency and low cost and is suitable for industrial production.
To achieve the purpose, the preparation method comprises the following steps:
(1) in the environment of organic solvent, dropwise adding organic solution containing isopropyl magnesium bromide into o-dibromo- [2.2] p-cyclophane under stirring;
(2) then adding copper catalyst CuX and diphenylphosphine chloride, heating to reflux reaction, adding water for quenching after the reaction is finished, adding dichloromethane and ammonia water for washing and separating liquid, drying, distilling and crystallizing to obtain an intermediate 4, 12-bis (diphenylphosphino) - [2.2] -p-cyclophane;
(3) and adding tartaric acid into the intermediate for resolution, and carrying out reduction reaction to obtain chiral 4, 12-bis (diphenylphosphino) - [2.2] -p-cyclophane.
In a preferred embodiment of the present invention, in step (1), the organic solvent is one or more selected from tetrahydrofuran, toluene, 2-methyltetrahydrofuran and xylene.
In a preferred embodiment of the present invention, the copper catalyst CuX is selected from at least one of cuprous chloride (CuCl), cuprous bromide (CuBr), cuprous iodide (CuI).
In a preferred embodiment of the invention, the molar ratio of isopropyl magnesium bromide to o-dibromo- [2.2] to cyclophane is 1.5:1 to 2.5: 1.
In a preferred embodiment of the invention, the dropping temperature of the isopropyl magnesium bromide in the step (1) is 20-60 ℃, and preferably, the dropping temperature is 50-60 ℃.
In a preferred embodiment of the present invention, the temperature of the heating to reflux reaction in step (2) is in the range of 65-80 deg.C
In a preferred embodiment of the present invention, n-heptane is added for crystallization in step (2).
In a preferred embodiment of the present invention, in step (3), after the resolution of tartaric acid, trichlorosilane is added for reduction reaction.
In a preferred embodiment of the present invention, at least step (1) of the reaction of the present invention is carried out under the protection of a protective gas, including but not limited to nitrogen, argon, helium.
Preferably, the preparation method of the 4, 12-bis (diphenyloxide) - [2.2] -p-cyclophane chiral phosphine ligand comprises the following steps: under the protection of argon, adding o-dibromo- [2.2] p-cyclophane and tetrahydrofuran into a reactor, dropwise adding a tetrahydrofuran solution of isopropylmagnesium bromide under stirring, then adding a copper catalyst CuX and diphenylphosphonic chloride, heating to reflux for reaction, adding water for quenching after the reaction is finished, adding dichloromethane and ammonia water for washing, separating, drying, distilling, adding n-heptane for crystallization to obtain 4, 12-bis (diphenylphosphino) - [2.2] -p-cyclophane, and then splitting and reducing the intermediate by tartaric acid to obtain chiral 4, 12-bis (diphenylphosphino) - [2.2] -p-cyclophane.
Compared with the prior art, the method avoids using reagents with high risk and high cost, can realize reaction by using a simple and feasible Grignard exchange method, has the yield of over 85 percent, and is suitable for industrial production.
Drawings
FIG. 1A is a nuclear magnetic H-NMR spectrum of a product obtained by the preparation method of example 1 of the present invention.
FIG. 1B is a nuclear magnetic P-NMR spectrum of the product obtained by the preparation method of example 1 of the present invention.
FIG. 2A is a nuclear magnetic H-NMR spectrum of the product obtained by the preparation method of example 2 of the present invention.
FIG. 2B is a nuclear magnetic P-NMR spectrum of the product obtained by the preparation method of example 2 of the present invention.
FIG. 3A is a nuclear magnetic H-NMR spectrum of the product obtained by the preparation method of example 3 of the present invention.
FIG. 3B is a nuclear magnetic P-NMR spectrum of the product obtained by the preparation method of example 3 of the present invention.
FIG. 4A is a nuclear magnetic H-NMR spectrum of the product obtained by the preparation method of example 4 of the present invention.
FIG. 4B is a nuclear magnetic P-NMR spectrum of the product obtained by the preparation method of example 4 of the present invention.
Detailed Description
For the sake of understanding, the present invention will be described in detail below by way of specific examples. It is to be expressly understood that the description is illustrative only and is not intended as a definition of the limits of the invention. Many variations and modifications of the present invention will be apparent to those skilled in the art in light of the teachings of this specification.
Example 1
Under the protection of argon, o-dibromo- [2.2] is added into a reactor]Adding a tetrahydrofuran solution (1.5L,1.5mol) of magnesium isopropoxide bromide into cyclophane (366g,1mol) and 1.5L tetrahydrofuran under stirring at 30 ℃, reacting at the temperature of 30 ℃, then adding cuprous chloride (99g,1mol) and diphenylphosphonic chloride (260g,1.1mol), heating to reflux reaction, adding water for quenching after the reaction is finished, adding dichloromethane and ammonia water for washing, separating, drying, distilling, adding n-heptane for crystallization to obtain 4, 12-bis (diphenylphosphino) - [2.2] 4]P-cyclophane (517g, 85%),31PNMR(δ，CDCl3)23.56ppm,23.18 ppm. The intermediate is resolved by D-tartaric acid, and reduction reaction is carried out by adding reducing agent trichlorosilane hydrogen to obtain R-4, 12-bis (diphenylphosphine) - [2.2]]P-cycloparaffin with a melting point of 225.1-225.6 ℃, and nuclear magnetism H-NMR of the product, wherein P-NMR is shown in attached figures 1A and 1B.
Example 2
Under the protection of argon, o-dibromo- [2.2] p-cyclophane (366g,1mol) and 1.5L tetrahydrofuran are added into a reactor, a tetrahydrofuran solution (1.5L,1.5mol) of magnesium isopropoxide bromide is added dropwise under stirring at 30 ℃, reaction is carried out at the temperature of 30 ℃, then cuprous iodide (190g,1mol) and diphenylphosphonic chloride (260g,1.1mol) are added, the temperature is raised to reflux reaction, water is added for quenching after the reaction is finished, dichloromethane and ammonia water are added for washing, separating, drying, distilling, and n-heptane is added for crystallization to obtain 4, 12-bis (diphenylphosphine oxide) - [2.2] -p-cyclophane (535g, 88%). The intermediate is resolved by D-tartaric acid, and is added with a reducing agent of trichlorosilane hydrogen to carry out reduction reaction to obtain R-4, 12-bis (diphenylphosphino) - [2.2] -p-cyclophane, and the melting point is as follows: 222.6-223.0 ℃. The nuclear magnetism H-NMR and P-NMR of the product are shown in the attached figures 2A and 2B.
Example 3
Under the protection of argon, o-dibromo- [2.2] p-cyclophane (366g,1mol) and 1.5L tetrahydrofuran are added into a reactor, a tetrahydrofuran solution (2.5L,2.5mol) of magnesium isopropoxide bromide is added dropwise under stirring at 30 ℃, reaction is carried out at the temperature of 30 ℃, then cuprous iodide (190g,1mol) and diphenylphosphonic chloride (260g,1.1mol) are added, the temperature is raised to reflux reaction, water is added for quenching after the reaction is finished, dichloromethane and ammonia water are added for washing, separating, drying, distilling, and n-heptane is added for crystallization to obtain 4, 12-bis (diphenylphosphine oxide) - [2.2] -p-cyclophane (560g, 92%). The intermediate is resolved by D-tartaric acid, and is added with a reducing agent of trichlorosilane hydrogen to carry out reduction reaction to obtain R-4, 12-bis (diphenylphosphino) - [2.2] -p-cyclophane, and the melting point is as follows: 222.6-223.4 ℃. The nuclear magnetism H-NMR and P-NMR of the product are shown in the attached figures 3A and 3B.
Example 4
Under the protection of argon, o-dibromo- [2.2] p-cycloparaffin (366g,1mol) and 1.5L tetrahydrofuran are added into a reactor, a tetrahydrofuran solution (2.5L,2.5mol) of magnesium isopropoxide bromide is added dropwise under stirring at 55 ℃, reaction is carried out at the temperature of 30 ℃, then cuprous iodide (190g,1mol) and diphenylphosphonic chloride (260g,1.1mol) are added, the temperature is raised to reflux reaction, water is added for quenching after the reaction is finished, dichloromethane and ammonia water are added for washing, separating liquid is washed, drying and distillation are carried out, n-heptane is added for crystallization, and 4, 12-bis (diphenylphosphine oxide) - [2.2] -p-cycloparaffin (572g, 94%) is obtained. The intermediate is resolved by D-tartaric acid, and is added with a reducing agent of trichlorosilane hydrogen to carry out reduction reaction to obtain R-4, 12-bis (diphenylphosphino) - [2.2] -p-cyclophane, and the melting point is as follows: 223.7-224.1 ℃. The nuclear magnetism H-NMR and P-NMR of the product are shown in figures 4A and 4B.
The above examples are only for illustrating the technical idea and features of the present invention, and the purpose thereof is to enable those skilled in the art to understand the content of the present invention and implement the present invention, and not to limit the protection scope of the present invention. All equivalent changes and modifications made according to the spirit of the present invention should be covered within the protection scope of the present invention.
Claims (8)
1. A preparation method of 4, 12-bis (diphenylphosphino) - [2.2] -p-cyclophane is characterized by comprising the following steps:
(1) in the environment of organic solvent, dropwise adding organic solution containing isopropyl magnesium bromide into o-dibromo- [2.2] p-cyclophane under stirring;
(2) then adding copper catalyst CuX and diphenylphosphine chloride, heating to reflux reaction, adding water for quenching after the reaction is finished, adding dichloromethane and ammonia water for washing and separating liquid, drying, distilling and crystallizing to obtain an intermediate 4, 12-bis (diphenylphosphino) - [2.2] -p-cyclophane;
(3) and adding tartaric acid into the intermediate for resolution, and carrying out reduction reaction to obtain chiral 4, 12-bis (diphenylphosphino) - [2.2] -p-cyclophane.
2. The preparation method according to claim 1, wherein in the step (1), the organic solvent is one or more selected from tetrahydrofuran, toluene, 2-methyltetrahydrofuran and xylene.
3. The method according to claim 1, wherein the copper catalyst CuX is at least one selected from the group consisting of cuprous chloride, cuprous bromide and cuprous iodide.
4. The preparation method according to claim 1, wherein the molar ratio of isopropyl magnesium bromide to o-dibromo- [2.2] to cyclophane is 1.5:1 to 2.5: 1.
5. The preparation method according to claim 1, wherein the dropping temperature of the isopropyl magnesium bromide in the step (1) is 20-60 ℃.
6. The method according to claim 1, wherein the temperature of the step (2) is raised to a temperature in the range of 65 to 80 ℃ for the reflux reaction.
7. The production method according to claim 1, wherein n-heptane is added for crystallization in the step (2).
8. The process according to claim 1, wherein in the step (3), after the resolution of tartaric acid, trichlorosilane is added to perform a reduction reaction.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN112094294A (en) * | 2020-11-10 | 2020-12-18 | 江苏欣诺科催化剂有限公司 | Synthesis method of bis (dicyclohexylphosphine) alkane |
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| KAREN DAMIAN等: "Palladium-catalysed P–C bond forming reactions between diphenylphosphine and ortho-substituted aryl bromides", 《APPL. ORGANOMETAL. CHEM.》 * |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112094294A (en) * | 2020-11-10 | 2020-12-18 | 江苏欣诺科催化剂有限公司 | Synthesis method of bis (dicyclohexylphosphine) alkane |
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