CN101445518B - Preparation method of phosphine ligand - Google Patents
Preparation method of phosphine ligand Download PDFInfo
- Publication number
- CN101445518B CN101445518B CN200810207617A CN200810207617A CN101445518B CN 101445518 B CN101445518 B CN 101445518B CN 200810207617 A CN200810207617 A CN 200810207617A CN 200810207617 A CN200810207617 A CN 200810207617A CN 101445518 B CN101445518 B CN 101445518B
- Authority
- CN
- China
- Prior art keywords
- phosphine ligand
- preparation
- phosphine part
- grignard reagent
- ether
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 title claims abstract description 54
- 238000002360 preparation method Methods 0.000 title claims abstract description 20
- 229910000073 phosphorus hydride Inorganic materials 0.000 title abstract description 16
- 239000003446 ligand Substances 0.000 title abstract description 15
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 claims abstract description 22
- 239000007818 Grignard reagent Substances 0.000 claims abstract description 18
- 150000004795 grignard reagents Chemical class 0.000 claims abstract description 12
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 claims abstract description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 9
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 28
- 238000006243 chemical reaction Methods 0.000 claims description 28
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 16
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims description 8
- 239000003153 chemical reaction reagent Substances 0.000 claims description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 4
- 235000019270 ammonium chloride Nutrition 0.000 claims description 4
- 238000001035 drying Methods 0.000 claims description 4
- DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 claims description 4
- 239000012074 organic phase Substances 0.000 claims description 4
- 229920006395 saturated elastomer Polymers 0.000 claims description 4
- 238000010898 silica gel chromatography Methods 0.000 claims description 4
- 238000003756 stirring Methods 0.000 claims description 4
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 claims description 3
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 claims description 3
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 claims description 3
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 3
- 239000000203 mixture Substances 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- 125000001033 ether group Chemical group 0.000 claims description 2
- 238000010438 heat treatment Methods 0.000 claims description 2
- 238000010992 reflux Methods 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 abstract description 21
- 238000000034 method Methods 0.000 abstract description 14
- 125000003107 substituted aryl group Chemical group 0.000 abstract description 6
- 125000003118 aryl group Chemical group 0.000 abstract description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 abstract description 4
- 125000003545 alkoxy group Chemical group 0.000 abstract description 4
- 229910052801 chlorine Inorganic materials 0.000 abstract description 4
- 239000000460 chlorine Substances 0.000 abstract description 4
- 229910052731 fluorine Inorganic materials 0.000 abstract description 4
- 239000011737 fluorine Substances 0.000 abstract description 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 abstract description 3
- 239000004305 biphenyl Substances 0.000 abstract description 3
- 150000002367 halogens Chemical group 0.000 abstract description 3
- 230000003197 catalytic effect Effects 0.000 abstract description 2
- 238000005859 coupling reaction Methods 0.000 abstract description 2
- 238000009776 industrial production Methods 0.000 abstract description 2
- 125000001424 substituent group Chemical group 0.000 abstract description 2
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 abstract 2
- 125000005841 biaryl group Chemical group 0.000 abstract 2
- 230000009257 reactivity Effects 0.000 abstract 1
- 238000000926 separation method Methods 0.000 abstract 1
- -1 biaryl hydro carbons Chemical class 0.000 description 18
- 150000005347 biaryls Chemical group 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 238000006555 catalytic reaction Methods 0.000 description 9
- 229930195733 hydrocarbon Natural products 0.000 description 9
- WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 8
- 239000004215 Carbon black (E152) Substances 0.000 description 8
- 229910052759 nickel Chemical class 0.000 description 8
- JVZRCNQLWOELDU-UHFFFAOYSA-N 4-Phenylpyridine Chemical compound C1=CC=CC=C1C1=CC=NC=C1 JVZRCNQLWOELDU-UHFFFAOYSA-N 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- HWXIHQKPOSGKHT-UHFFFAOYSA-N (2-diphenylphosphanylphenyl)-phenylmethanol Chemical compound C=1C=CC=C(P(C=2C=CC=CC=2)C=2C=CC=CC=2)C=1C(O)C1=CC=CC=C1 HWXIHQKPOSGKHT-UHFFFAOYSA-N 0.000 description 4
- CUJRVFIICFDLGR-UHFFFAOYSA-N acetylacetonate Chemical compound CC(=O)[CH-]C(C)=O CUJRVFIICFDLGR-UHFFFAOYSA-N 0.000 description 4
- 229940067107 phenylethyl alcohol Drugs 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- QARVLSVVCXYDNA-UHFFFAOYSA-N phenyl bromide Natural products BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 description 3
- ZZLCFHIKESPLTH-UHFFFAOYSA-N 4-Methylbiphenyl Chemical group C1=CC(C)=CC=C1C1=CC=CC=C1 ZZLCFHIKESPLTH-UHFFFAOYSA-N 0.000 description 2
- BSDGZUDFPKIYQG-UHFFFAOYSA-N 4-bromopyridine Chemical compound BrC1=CC=NC=C1 BSDGZUDFPKIYQG-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-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
- 125000000217 alkyl group Chemical group 0.000 description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 2
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 2
- 239000004327 boric acid Substances 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- XLJMAIOERFSOGZ-UHFFFAOYSA-N cyanic acid Chemical compound OC#N XLJMAIOERFSOGZ-UHFFFAOYSA-N 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 229910052723 transition metal Inorganic materials 0.000 description 2
- 150000003624 transition metals Chemical class 0.000 description 2
- LVEYOSJUKRVCCF-UHFFFAOYSA-N 1,3-Bis(diphenylphosphino)propane Substances C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCP(C=1C=CC=CC=1)C1=CC=CC=C1 LVEYOSJUKRVCCF-UHFFFAOYSA-N 0.000 description 1
- ABGJKANJAGHUMH-UHFFFAOYSA-N 1-[4-(3,5-dimethylphenyl)phenyl]-3,5-dimethylbenzene Chemical group CC1=CC(C)=CC(C=2C=CC(=CC=2)C=2C=C(C)C=C(C)C=2)=C1 ABGJKANJAGHUMH-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- VMQMZMRVKUZKQL-UHFFFAOYSA-N Cu+ Chemical compound [Cu+] VMQMZMRVKUZKQL-UHFFFAOYSA-N 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
- 238000005577 Kumada cross-coupling reaction Methods 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 239000000400 angiotensin II type 1 receptor blocker Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Substances C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 230000000536 complexating effect Effects 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 239000002322 conducting polymer Substances 0.000 description 1
- 229920001940 conductive polymer Polymers 0.000 description 1
- 239000012954 diazonium Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 125000006575 electron-withdrawing group Chemical group 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- LELOWRISYMNNSU-UHFFFAOYSA-N hydrogen cyanide Chemical compound N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 239000004973 liquid crystal related substance Substances 0.000 description 1
- 229910052748 manganese Inorganic materials 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000003003 phosphines Chemical class 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- YXFVVABEGXRONW-UHFFFAOYSA-N toluene Substances CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to a preparation method of phosphine ligand and a method for the phosphine ligand to catalyze and synthetize biaryl and derivatives thereof. The preparation method of the phosphine ligand comprises the following steps: 2-diphenyl phosphono benzaldehyde is used to react with a Grignard reagent, and the phosphine ligand is acquired; X in the Grignard reagent is halogen, and R is C1-C8 alkyl, aryl or substituted aryl; wherein, the substituted aryl is that one or multiple positions in number 2 to 6 positions of aromatic ring are substituted; and substituent is one or varieties in fluorine, chlorine, phenyl, C1-C8 alkyl and C1-C8 alkoxy. The invention discloses the method of using the phosphine ligand to jointly catalyze and synthetize the biaryl and the derivatives thereof with a nickel catalyst. The invention uses high catalytic activity of the phosphine ligand, TON is usually higher than 2500, and the phosphine ligand is easy to be prepared and suitable for industrial production. The phosphine ligand can be produced by the Grignard reagent and 2-diphenyl phosphono-containing benzaldehyde in the field without separation, and directly catalyze a coupling reaction; and furthermore, the reactivity of the phosphine ligand is not obviously reduced.
Description
Technical field
The present invention relates to a kind of synthetic biaryl of preparation method and catalysis thereof of phosphine part and the method for verivate thereof, be specifically related to the preparation method of one type of phosphine part, and the method for synthesizing biaryl and verivate thereof with this phosphine part and nickel catalyzator associating catalysis.
Background technology
The compound of biaryl hydro carbons is one type of function and broad-spectrum compound, is usually used in liquid crystal material and medicine intermediate.Such as: 3,4,3 ", 4 "-the tetramethyl-terphenyl just is used for conducting polymer composite, and 4 '-methyl diphenyl-2-formonitrile HCN is the midbody of sartans.
The compound method of biaryl commonly used has aryl diazonium salts, and reaction generates biaryl with aromatic hydrocarbons under copper (I) catalysis; This method does not have the sterically hindered biaryl more suitable to synthetic ortho position; The ortho position has when all electron-withdrawing group being arranged on steric hindrance or two phenyl ring, just is difficult to synthesize obtain required product with this method.
Another kind method is to use the Suzuki linked reaction; Be that fragrant boric acid or its ester generate biaryl with the halogenated aryl hydrocarbon linked reaction under the catalysis of transition metal, this method applicability is very wide, can tolerate a lot of functional groups; Catalyzer is with Pd (O), the Ni (O) of various part complexings; Even metal complexs such as Mn, Fe can catalysis should reaction, but the preparation of the phenylo boric acid of one of main raw material of its reaction or its ester difficulty relatively, price is higher; The catalyzer that uses all is homogeneous Pd catalyzer, and the recovery of catalyzer is difficulty.
Also use the Kumada linked reaction in the industry, promptly Grignard reagent generates biphenyl with halogeno-benzene reaction under the catalysis of transition metal since the industry that is prepared in of Grignard reagent to go up utilization more extensive, mostly its catalyzer is Ni catalyzer, low price.The system of catalyzer has a variety of, such as NiCl
2/ PPh
3, NiCl
2Dppp, NiCl
2Dppe, NiCl
2Dppf etc., they all use various Kumada linked reactions, and yield is good.
Summary of the invention
Technical problem to be solved by this invention is to provide a kind of high efficiency preparation method of phosphine part and one type of phosphine part product of acquisition.
Another technical problem to be solved by this invention is to provide a kind of above-mentioned phosphine part and nickel catalyzator associating catalysis Kumada reaction, method of synthetic biaryl and verivate thereof utilized.
The present invention solves the problems of the technologies described above the technical scheme of being taked: a kind of preparation method of phosphine part, obtain the phosphine part with 2-diphenylphosphine benzaldehyde dative formula reagent react, and reaction formula is:
Wherein, X is a halogen, and R is alkyl, phenyl or the substituted-phenyl of C1～C8, and substituted-phenyl is to have one or more positions to be substituted in 2～No. 6 positions of aromatic ring, and substituting group is one or more in fluorine, chlorine, phenyl, C1～C8 alkyl, the C1～C8 alkoxyl group.
On the basis of such scheme, a kind of concrete preparation method is provided: under nitrogen protection, 2-diphenylphosphine benzaldehyde is dissolved in the solvent, drips Grignard reagent under the stirring at room; The mol ratio of 2-diphenylphosphine benzaldehyde dative formula reagent is 1: 1.1～2, and heating reflux reaction 80～100 minutes is cooled to room temperature, pours in the cold saturated aqueous ammonium chloride; Use the extracted with diethyl ether water, merge organic phase, use anhydrous sodium sulfate drying; After concentrating, silica gel column chromatography separates, and gets the phosphine part.
Concrete, the mol ratio of 2-diphenylphosphine benzaldehyde dative formula reagent can be 1: 1.1,1.2,1.3,1.4,1.5,1.6,1.7,1.8,1.9 or 2.
On the basis of such scheme; In the process of preparation phosphine part; Described organic solvent can be ether, MTBE, THF, 2-methyltetrahydrofuran, isopropyl ether, dibutyl ether, 1, the mixture of one or more in the 2-glycol dimethyl ether etc.
To the phosphine part that above-mentioned preparation method obtains, its general structure is:
Wherein, R is alkyl, aryl or the substituted aryl of C1～C8, and substituted aryl is to have one or more positions to be substituted base in 2～No. 6 positions of aromatic ring to replace, and substituting group is one or more in fluorine, chlorine, phenyl, C1～C8 alkyl, the C1～C8 alkoxyl group.
To the method for synthetic biaryl of above-mentioned phosphine ligand catalysis and verivate thereof, be united catalyst with phosphine part and nickel catalyzator, catalysis halogenated aryl hydrocarbon and synthetic biaryl of phenyl grignard reagent reaction and verivate thereof.
On the basis of such scheme, halogenated aryl hydrocarbon, nickel catalyzator, phosphine part all are dissolved in the organic solution, under nitrogen protection; Add nickel catalyzator and phosphine ligand solution in the halogenated aryl hydrocarbon solution; Add phenyl grignard reagent solution reaction again, finish, obtain biaryl and verivate thereof to reacting.
On the basis of such scheme, the mol ratio of said halogenated aryl hydrocarbon, Grignard reagent, nickel catalyzator, phosphine part is: 1: (1.1～2): (0.0001～0.1): (0.0002～0.2).
Concrete, the mol ratio of halogenated aryl hydrocarbon, Grignard reagent, nickel catalyzator, phosphine part can for: 1: (1.1,1.2,1.3,1.5; 1.6,1.8,1.9 or 2): (0.0001,0.0005,0.001; 0.005,0.01,0.05 or 0.1): (0.0002,0.0005,0.001; 0.005,0.01,0.05,0.1,0.15 or 0.2).Ratio of greater inequality is: halogenated aryl hydrocarbon: Grignard reagent: nickel catalyzator: phosphine part=1: 1.2: 0.001: 0.002.
On the basis of such scheme; In the described halogenated aryl hydrocarbon; Halogenic substituent is fluorine, chlorine, bromine or iodine; Aromatic hydrocarbons can be phenyl, pyridine or substituted aryl, and substituted aryl is to have one, two or three position to be substituted base in 2～No. 6 positions of phenyl ring to replace, and this substituting group is one or more in cyanic acid, C1～C8 carbalkoxy, halogen, phenyl, C1～C8 alkyl, the C1～C8 alkoxyl group.
On the basis of such scheme, described organic solvent is ether, MTBE, THF, 2-methyltetrahydrofuran, isopropyl ether, dibutyl ether, 1, one or more mixtures such as grade in the ethers such as 2-glycol dimethyl ether.
On the basis of such scheme, described temperature of reaction is-20～100 ℃, preferred 10～20 ℃.
The invention has the beneficial effects as follows:
Use the catalytic activity of such part very high, TON is usually greater than 2500, and preparation easily is fit to industrial production.Many times, this type part can on-the-spotly be generated by Grignard reagent and 2-diphenylphosphine benzaldehyde, and needn't separate, direct catalyzed coupling reaction, and reactive behavior is not seen obvious reduction.
Embodiment
Embodiment 1
The preparation of phosphine ligand 1-(2-diphenylphosphino) phenylethyl alcohol:
Under nitrogen protection, the 250ml four-hole bottle adds 7.6g 2-diphenylphosphine benzaldehyde, 100ml THF, the anhydrous ether solution of Dropwise 5 0ml 1M methyl iodide Grignard reagent under 20 ℃ of stirrings; Dropwise, be heated to back flow reaction 90 minutes, reaction cooled is poured in the cold saturated aqueous ammonium chloride to room temperature; Use the extracted with diethyl ether water, merge organic phase, use anhydrous sodium sulfate drying, after concentrating; Silica gel column chromatography separates, and gets product, and the NMR data conform to document.
Reaction formula is:
The application of phosphine ligand 1-(2-diphenylphosphino) phenylethyl alcohol: preparation 4-methyl diphenyl
Under nitrogen protection, in the Schlenk bottle of 50ml, add 111mg 4-toluene fluoride, 20ml THF, 1.2ml catalyst n i (acac)
2(this solution is 25mg Ni (acac) with the tetrahydrofuran solution of phosphine ligand 1-(2-diphenylphosphino) phenylethyl alcohol
2, it is formulated that 32mg 1-(2-diphenylphosphino) phenylethyl alcohol is dissolved in the 12ml THF), the tetrahydrofuran solution (1M) of adding 1.1mlPhMgBr under the room temperature, gas phase is followed the tracks of, and adds the cancellation of 0.2ml methyl alcohol after reaction finishes and reacts; Conventional aftertreatment obtains the 4-methyl diphenyl, yield 94%, 1H NMR (CDCl3): 7.58-7.56 (m, 2H), 7.50-7.48 (m; 2H), and 7.44-7.40 (m, 2H), 7.33-7.30 (m, 1H); 7.25-7.24 (m, 2H), 2.39 (s, 3H).
Reaction formula is:
Embodiment 2
The preparation of phosphine part (2-diphenylphosphino phenyl) phenylcarbinol:
Under nitrogen protection, the 250ml four-hole bottle adds 7.6g 2-diphenylphosphine benzaldehyde, 100ml THF, the tetrahydrofuran solution (1M) of Dropwise 5 0ml bromobenzene Grignard reagent under 20 ℃ of stirrings; Dropwise, be heated to back flow reaction 90 minutes, reaction cooled is poured in the cold saturated aqueous ammonium chloride to room temperature; Use the extracted with diethyl ether water, merge organic phase, use anhydrous sodium sulfate drying; After concentrating, silica gel column chromatography separates, and gets product.
Reaction formula is:
The application of phosphine part (2-diphenylphosphino phenyl) phenylcarbinol: preparation 4-phenylpyridine
Method A: under nitrogen protection, the 500ml four-hole bottle adds 18g to the 4-bromopyridine, 2.355g (2-diphenylphosphino phenyl) phenylcarbinol, 0.82g Ni (acac)
2Catalyzer and 200ml THF, 20 ℃ of tetrahydrofuran solutions (1M) that drip 260ml bromobenzene grignard reagent down, 2.5h dropwises, and gas phase is followed the tracks of, and adds 2ml methyl alcohol cancellation reaction after reaction finishes, and conventional aftertreatment obtains the 4-phenylpyridine, yield 75%.
Method B: under nitrogen protection, the 500ml four-hole bottle adds 18g 4-bromopyridine, 1.856g (2-diphenylphosphino phenyl) phenylcarbinol, 0.82gNi (acac)
2Catalyzer and 200ml THF, 20 ℃ of tetrahydrofuran solutions (1M) that drip down 280ml bromobenzene grignard reagent, 2.5h add and finish, and gas phase is followed the tracks of, and the reaction back that finishes adds 2ml methyl alcohol cancellation reaction, and conventional aftertreatment obtains the 4-phenylpyridine, yield 75%.
Reaction formula is:
Claims (3)
1. the preparation method of a phosphine part obtains the phosphine part with 2-diphenylphosphine benzaldehyde Yu Geshi reagent react, and reaction formula is:
X is a halogen in the Grignard reagent, and R is a methyl or phenyl.
2. the preparation method of phosphine part according to claim 1 is characterized in that: under nitrogen protection, 2-diphenylphosphine benzaldehyde is dissolved in the solvent; Drip Grignard reagent under the stirring at room, the mol ratio of 2-diphenylphosphine benzaldehyde Yu Geshi reagent is 1: 1.1～2, heating reflux reaction 80～100 minutes; Be cooled to room temperature, pour in the cold saturated aqueous ammonium chloride, use the extracted with diethyl ether water; Merge organic phase, use anhydrous sodium sulfate drying, after concentrating; Silica gel column chromatography separates, and gets the phosphine part.
3. the preparation method of phosphine part according to claim 2; It is characterized in that: described solvent is ether, MTBE, THF, 2-methyltetrahydrofuran, isopropyl ether, dibutyl ether, 1, the mixture of one or more in the 2-glycol dimethyl ether.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200810207617A CN101445518B (en) | 2008-12-23 | 2008-12-23 | Preparation method of phosphine ligand |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200810207617A CN101445518B (en) | 2008-12-23 | 2008-12-23 | Preparation method of phosphine ligand |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101445518A CN101445518A (en) | 2009-06-03 |
| CN101445518B true CN101445518B (en) | 2012-09-05 |
Family
ID=40741431
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN200810207617A Active CN101445518B (en) | 2008-12-23 | 2008-12-23 | Preparation method of phosphine ligand |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101445518B (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006085628A1 (en) * | 2005-02-08 | 2006-08-17 | The University Of Tokyo | Method for producing compound through coupling |
-
2008
- 2008-12-23 CN CN200810207617A patent/CN101445518B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006085628A1 (en) * | 2005-02-08 | 2006-08-17 | The University Of Tokyo | Method for producing compound through coupling |
Non-Patent Citations (2)
| Title |
|---|
| Naohiko Yoshikai et al..Nickel-Catalyzed Cross-Coupling Reaction of Aryl Fluorides and Chlorides with Grignard Reagents under Nickel/Magnesium Bimetallic Cooperation.《Journal of the American Chemical Society》.2005,第127卷(第51期),17978-17979,S2-S3. * |
| Sven Sjovall et al..Cyclometalation Reactions on Rhodium(I). Evidence for a Chelate Effect and Competing C-H and C-O Oxidative Additions.《Organometallics》.2001,第20卷(第23期),4919-4926. * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101445518A (en) | 2009-06-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103804413B (en) | Three Phosphine ligands preparation method of biphenyl and progressively replace PPh in hydroformylation3Application | |
| EP2492274B1 (en) | 2,4,6- or 2,6-alkoxyphenyl dialkylphosphine, tetrafluoroborate and use thereof | |
| CN101787042B (en) | Copper-nitrogen compound and application thereof | |
| Liu et al. | A Highly Active Pd (II) Complex with 1‐Tritylimidazole Ligand for Suzuki‐Miyaura and Heck Coupling Reactions | |
| Flanagan et al. | The preparation and resolution of 2-(2-pyridyl)-and 2-(2-pyrazinyl)-Quinazolinap and their application in palladium-catalysed allylic substitution | |
| Ju et al. | Palladium-catalyzed cross-coupling of trimethoxysilylbenzene with aryl bromides and chlorides using phosphite ligands | |
| CN102125875A (en) | Application of cyclopalladated ferrocenylimine-phosphine adduct in synthesis of asymmetric biaryl compound | |
| CN101445518B (en) | Preparation method of phosphine ligand | |
| CN102746124A (en) | Method for preparing substituted alkene | |
| CN101195641A (en) | Novel phosphine ligand, production and uses in catalytic reaction thereof | |
| CN101284753B (en) | Self-coupling reaction method of manganses-catalyzed and oxidized chlorobenzene grignard reagent | |
| Guo et al. | The air-stable and highly efficient P, N-chelated palladium (II) complexes as catalysts for the Suzuki cross-coupling reaction at room temperature | |
| CN101643378A (en) | Method for synthesizing aryl-linking compound | |
| CN101952253B (en) | Process for preparing substituted biphenylanilides | |
| CN109369715A (en) | A method of synthesis di-t-butyl phosphine biphenyl compound | |
| CN109970773A (en) | A kind of new synthetic method of N-Boc-1,2,5,6- tetrahydropyridine -4- pinacol borate | |
| CN114907404B (en) | 5- (2- (Disubstituted phosphino) phenyl) -1-alkyl-1H-pyrazolyl phosphine ligand and preparation method and application thereof | |
| CN101967075A (en) | Method for synthesizing terminal alkyne compound by using 3-aryl-2,3-dibromopropionic acid | |
| CN102153483B (en) | Axial chirality vicinal diamine compound and preparation method thereof | |
| CN101503625B (en) | Preparation method of 1,2-diaryl ethine liquid crystal | |
| JPWO2006085628A1 (en) | Method for producing coupling compound | |
| CN107382734A (en) | The Suzuki coupling reactions of the ammino palladium chtalyst nitro-chlorobenzene of dichloro two | |
| Yu et al. | Synthesis and application of novel ionic phosphine ligands with a cobaltocenium backbone | |
| CN112979513A (en) | Chiral sulfoxide containing styrene monomer and preparation method thereof | |
| CN114805017B (en) | Preparation method of 2-fluoro-1, 5-hexadiene compound |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| ASS | Succession or assignment of patent right |
Owner name: SHANGHAI LIKE CHEMISTRY TECHNOLOGY CO., LTD. Effective date: 20140909 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| COR | Change of bibliographic data |
Free format text: CORRECT: ADDRESS; FROM: 200050 PUTUO, SHANGHAI TO: 201202 PUDONG NEW AREA, SHANGHAI |
|
| TR01 | Transfer of patent right |
Effective date of registration: 20140909 Address after: 201202, Shanghai, Pudong New Area, South Sichuan Highway No. 2, building 206, room 3397 Patentee after: Shanghai Record Pharmaceuticals Ltd. Patentee after: SHANGHAI RECORDCHEM TECHNOLOGY CO.,LTD. Address before: 200050 No. 799, Dunhuang Road, Shanghai, Putuo District Patentee before: Shanghai Record Pharmaceuticals Ltd. |
|
| EE01 | Entry into force of recordation of patent licensing contract |
Application publication date: 20090603 Assignee: Shanghai Puchuang Longke Finance Leasing Co.,Ltd. Assignor: Shanghai Record Pharmaceuticals Ltd. Contract record no.: X2019310000029 Denomination of invention: Preparation method of chiral ferrocene phosphine ligand Granted publication date: 20120905 License type: Exclusive License Record date: 20191226 |
|
| EE01 | Entry into force of recordation of patent licensing contract | ||
| PE01 | Entry into force of the registration of the contract for pledge of patent right | ||
| PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: Preparation method of chiral ferrocene phosphine ligand Effective date of registration: 20191227 Granted publication date: 20120905 Pledgee: Shanghai Puchuang Longke Finance Leasing Co.,Ltd. Pledgor: Shanghai Record Pharmaceuticals Ltd. Registration number: Y2019310000037 |
|
| TR01 | Transfer of patent right |
Effective date of registration: 20201126 Address after: Room 8173, building C, 555 Dongchuan Road, Minhang District, Shanghai Patentee after: SHANGHAI RECORDCHEM TECHNOLOGY CO.,LTD. Address before: 201202, Shanghai, Pudong New Area, South Sichuan Highway No. 2, building 206, room 3397 Patentee before: Shanghai Record Pharmaceuticals Ltd. Patentee before: SHANGHAI RECORDCHEM TECHNOLOGY Co.,Ltd. |
|
| TR01 | Transfer of patent right | ||
| PC01 | Cancellation of the registration of the contract for pledge of patent right | ||
| PC01 | Cancellation of the registration of the contract for pledge of patent right |
Date of cancellation: 20201228 Granted publication date: 20120905 Pledgee: Shanghai Puchuang Longke Finance Leasing Co.,Ltd. Pledgor: Shanghai Record Pharmaceuticals Ltd. Registration number: Y2019310000037 |
|
| EC01 | Cancellation of recordation of patent licensing contract | ||
| EC01 | Cancellation of recordation of patent licensing contract |
Assignee: Shanghai Puchuang Longke Finance Leasing Co.,Ltd. Assignor: Shanghai Record Pharmaceuticals Ltd. Contract record no.: X2019310000029 Date of cancellation: 20210108 |
|
| PE01 | Entry into force of the registration of the contract for pledge of patent right | ||
| PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: Preparation method of phosphine ligand Effective date of registration: 20211012 Granted publication date: 20120905 Pledgee: Industrial Bank Co.,Ltd. Shanghai Hongkou sub branch Pledgor: SHANGHAI RECORDCHEM TECHNOLOGY Co.,Ltd. Registration number: Y2021980010591 |
|
| PC01 | Cancellation of the registration of the contract for pledge of patent right |
Date of cancellation: 20230530 Granted publication date: 20120905 Pledgee: Industrial Bank Co.,Ltd. Shanghai Hongkou sub branch Pledgor: SHANGHAI RECORDCHEM TECHNOLOGY CO.,LTD. Registration number: Y2021980010591 |
|
| PC01 | Cancellation of the registration of the contract for pledge of patent right |