CN116396327A - Preparation method of high-purity aromatic phosphine oxide compound - Google Patents
Preparation method of high-purity aromatic phosphine oxide compound Download PDFInfo
- Publication number
- CN116396327A CN116396327A CN202211692535.0A CN202211692535A CN116396327A CN 116396327 A CN116396327 A CN 116396327A CN 202211692535 A CN202211692535 A CN 202211692535A CN 116396327 A CN116396327 A CN 116396327A
- Authority
- CN
- China
- Prior art keywords
- phosphine oxide
- oxide compound
- diphenyl
- aryl
- peroxide
- 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.)
- Pending
Links
- -1 aromatic phosphine oxide compound Chemical class 0.000 title claims abstract description 47
- 238000002360 preparation method Methods 0.000 title claims abstract description 25
- 238000000034 method Methods 0.000 claims abstract description 40
- 238000004440 column chromatography Methods 0.000 claims abstract description 38
- 238000000746 purification Methods 0.000 claims abstract description 31
- 150000001875 compounds Chemical class 0.000 claims abstract description 28
- 239000000047 product Substances 0.000 claims abstract description 21
- 230000008569 process Effects 0.000 claims abstract description 18
- 150000002978 peroxides Chemical class 0.000 claims abstract description 13
- 239000007800 oxidant agent Substances 0.000 claims abstract description 12
- 239000012043 crude product Substances 0.000 claims abstract description 10
- 239000003513 alkali Substances 0.000 claims abstract description 9
- 230000001590 oxidative effect Effects 0.000 claims abstract description 9
- 238000005859 coupling reaction Methods 0.000 claims abstract description 7
- 150000002989 phenols Chemical class 0.000 claims abstract description 7
- 230000008878 coupling Effects 0.000 claims abstract description 3
- 238000010168 coupling process Methods 0.000 claims abstract description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 172
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 140
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 35
- 239000004305 biphenyl Substances 0.000 claims description 31
- 235000010290 biphenyl Nutrition 0.000 claims description 31
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 31
- 125000006267 biphenyl group Chemical group 0.000 claims description 30
- 239000002904 solvent Substances 0.000 claims description 28
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 27
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 27
- AUONHKJOIZSQGR-UHFFFAOYSA-N oxophosphane Chemical compound P=O AUONHKJOIZSQGR-UHFFFAOYSA-N 0.000 claims description 26
- 239000012046 mixed solvent Substances 0.000 claims description 23
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 23
- 125000003118 aryl group Chemical group 0.000 claims description 20
- 239000003480 eluent Substances 0.000 claims description 19
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 18
- 238000000859 sublimation Methods 0.000 claims description 18
- 230000008022 sublimation Effects 0.000 claims description 18
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 16
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 15
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 13
- 238000003756 stirring Methods 0.000 claims description 12
- 125000001072 heteroaryl group Chemical group 0.000 claims description 8
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims description 7
- 238000006069 Suzuki reaction reaction Methods 0.000 claims description 7
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 claims description 7
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- 229910052763 palladium Inorganic materials 0.000 claims description 6
- 238000005406 washing Methods 0.000 claims description 6
- 239000003960 organic solvent Substances 0.000 claims description 5
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 4
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 4
- 239000003054 catalyst Substances 0.000 claims description 4
- XXQBEVHPUKOQEO-UHFFFAOYSA-N potassium superoxide Chemical compound [K+].[K+].[O-][O-] XXQBEVHPUKOQEO-UHFFFAOYSA-N 0.000 claims description 4
- 239000008096 xylene Substances 0.000 claims description 4
- BMIBJCFFZPYJHF-UHFFFAOYSA-N 2-methoxy-5-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine Chemical compound COC1=NC=C(C)C=C1B1OC(C)(C)C(C)(C)O1 BMIBJCFFZPYJHF-UHFFFAOYSA-N 0.000 claims description 3
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims description 3
- 125000003107 substituted aryl group Chemical group 0.000 claims description 3
- 239000004342 Benzoyl peroxide Substances 0.000 claims description 2
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 claims description 2
- 235000019400 benzoyl peroxide Nutrition 0.000 claims description 2
- 239000004327 boric acid Substances 0.000 claims description 2
- LSXWFXONGKSEMY-UHFFFAOYSA-N di-tert-butyl peroxide Chemical compound CC(C)(C)OOC(C)(C)C LSXWFXONGKSEMY-UHFFFAOYSA-N 0.000 claims description 2
- 230000032050 esterification Effects 0.000 claims description 2
- 238000005886 esterification reaction Methods 0.000 claims description 2
- 238000003818 flash chromatography Methods 0.000 claims description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 238000001953 recrystallisation Methods 0.000 claims description 2
- PFUVRDFDKPNGAV-UHFFFAOYSA-N sodium peroxide Chemical compound [Na+].[Na+].[O-][O-] PFUVRDFDKPNGAV-UHFFFAOYSA-N 0.000 claims description 2
- 239000002994 raw material Substances 0.000 claims 1
- 238000000926 separation method Methods 0.000 abstract description 9
- 239000000463 material Substances 0.000 abstract description 3
- 230000002195 synergetic effect Effects 0.000 abstract description 3
- 239000004065 semiconductor Substances 0.000 abstract description 2
- 239000012044 organic layer Substances 0.000 description 28
- 238000006243 chemical reaction Methods 0.000 description 21
- 239000007787 solid Substances 0.000 description 18
- 239000000243 solution Substances 0.000 description 16
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 15
- 238000004128 high performance liquid chromatography Methods 0.000 description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 11
- 238000007670 refining Methods 0.000 description 10
- XAMQTCWAEFIFRO-UHFFFAOYSA-N 3-diphenoxyphosphorylphenol Chemical compound OC1=CC=CC(P(=O)(OC=2C=CC=CC=2)OC=2C=CC=CC=2)=C1 XAMQTCWAEFIFRO-UHFFFAOYSA-N 0.000 description 9
- 238000005481 NMR spectroscopy Methods 0.000 description 9
- YMWUJEATGCHHMB-DICFDUPASA-N dichloromethane-d2 Chemical group [2H]C([2H])(Cl)Cl YMWUJEATGCHHMB-DICFDUPASA-N 0.000 description 9
- 239000012065 filter cake Substances 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 6
- IVDFJHOHABJVEH-UHFFFAOYSA-N pinacol Chemical compound CC(C)(O)C(C)(C)O IVDFJHOHABJVEH-UHFFFAOYSA-N 0.000 description 6
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical group [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 4
- 238000004821 distillation Methods 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- GZZLAPUQZCXKKT-UHFFFAOYSA-N 1-bromo-3-diphenylphosphorylbenzene Chemical compound BrC1=CC=CC(P(=O)(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 GZZLAPUQZCXKKT-UHFFFAOYSA-N 0.000 description 2
- HNZUKQQNZRMNGS-UHFFFAOYSA-N 2-(3-bromophenyl)-4,6-diphenyl-1,3,5-triazine Chemical compound BrC1=CC=CC(C=2N=C(N=C(N=2)C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 HNZUKQQNZRMNGS-UHFFFAOYSA-N 0.000 description 2
- PJEVNPPSOPLEGS-UHFFFAOYSA-N 2-[3-(10-bromoanthracen-9-yl)phenyl]-4,6-diphenyl-1,3,5-triazine Chemical compound BrC1=C2C=CC=CC2=C(C2=CC=CC=C12)C=1C=C(C=CC=1)C1=NC(=NC(=N1)C1=CC=CC=C1)C1=CC=CC=C1 PJEVNPPSOPLEGS-UHFFFAOYSA-N 0.000 description 2
- OADZHFGJIVKDJN-UHFFFAOYSA-N 3-bromo-1,10-phenanthroline Chemical compound C1=CN=C2C3=NC=C(Br)C=C3C=CC2=C1 OADZHFGJIVKDJN-UHFFFAOYSA-N 0.000 description 2
- LCJYRCMTHQJILZ-UHFFFAOYSA-N 3-bromo-9-phenyl-6-(9-phenylcarbazol-3-yl)carbazole Chemical compound C12=CC=C(C=3C=C4C5=CC=CC=C5N(C=5C=CC=CC=5)C4=CC=3)C=C2C2=CC(Br)=CC=C2N1C1=CC=CC=C1 LCJYRCMTHQJILZ-UHFFFAOYSA-N 0.000 description 2
- DPZQXKVORQTNMQ-UHFFFAOYSA-N 3-diphenylphosphorylphenol Chemical compound OC1=CC=CC(P(=O)(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 DPZQXKVORQTNMQ-UHFFFAOYSA-N 0.000 description 2
- 230000001476 alcoholic effect Effects 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 2
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 238000001819 mass spectrum Methods 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
- 235000011056 potassium acetate Nutrition 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000004289 sodium hydrogen sulphite Substances 0.000 description 2
- 235000010265 sodium sulphite Nutrition 0.000 description 2
- OBWURDWSVVRXLE-UHFFFAOYSA-N (3-bromophenyl)-diphenylphosphane Chemical compound BrC1=CC=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 OBWURDWSVVRXLE-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- YFPJFKYCVYXDJK-UHFFFAOYSA-N Diphenylphosphine oxide Chemical compound C=1C=CC=CC=1[P+](=O)C1=CC=CC=C1 YFPJFKYCVYXDJK-UHFFFAOYSA-N 0.000 description 1
- AFCIMSXHQSIHQW-UHFFFAOYSA-N [O].[P] Chemical compound [O].[P] AFCIMSXHQSIHQW-UHFFFAOYSA-N 0.000 description 1
- 239000005456 alcohol based solvent Substances 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 239000007859 condensation product Substances 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- MPQXHAGKBWFSNV-UHFFFAOYSA-N oxidophosphanium Chemical group [PH3]=O MPQXHAGKBWFSNV-UHFFFAOYSA-N 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- WLPUWLXVBWGYMZ-UHFFFAOYSA-N tricyclohexylphosphine Chemical compound C1CCCCC1P(C1CCCCC1)C1CCCCC1 WLPUWLXVBWGYMZ-UHFFFAOYSA-N 0.000 description 1
Images
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
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/50—Organo-phosphines
- C07F9/53—Organo-phosphine oxides; Organo-phosphine thioxides
- C07F9/5325—Aromatic phosphine oxides or thioxides (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
- C07F9/547—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
- C07F9/572—Five-membered rings
- C07F9/5728—Five-membered rings condensed with carbocyclic rings or carbocyclic ring systems
-
- 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
- C07F9/6515—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having three nitrogen atoms as the only ring hetero atoms
- C07F9/6521—Six-membered 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
- C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
- C07F9/65616—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings containing the ring system having three or more than three double bonds between ring members or between ring members and non-ring members, e.g. purine or analogs
Landscapes
- 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)
Abstract
The invention belongs to the technical field of application of organic semiconductor materials, and discloses a preparation method of a high-purity aromatic phosphine oxide compound, the structural formula of which is shown as formula I (formula I)
). The main process of the purification preparation of the compounds comprises the following steps: (1) Using arylphosphinoxyboronates
With bromoaryl derivatives Br-R 2 Is a coupling reaction of (2); (2) Br-R 2 The polarity of the product is less than that of the target product (formula I), and the product is separated and removed by column chromatography; (3) For the purpose of(1) And (2) the coupling crude product obtained in the step (2) is converted into a phenol derivative which is easy to separate through the synergistic effect of a peroxide oxidant and alkali, so as to achieve the aim of purification and separation.
Description
Technical Field
The invention belongs to the technical field of application of organic semiconductor materials, and particularly relates to a preparation method of a high-purity aromatic phosphine oxide compound.
Background
The aryl phosphine oxide group has the characteristics of rigidity, three-dimensional molecular structure and strong electron withdrawing, can be conveniently used for constructing an amorphous organic functional material, and also has reversible electrochemical reduction property. Chinese patent No. 103374040B discloses a preparation method of a functional compound containing triaryl phosphorus oxygen and nitrogen heterocyclic groups, namely coupling aryl phosphine oxide boric acid ester and halogenated nitrogen heterocyclic ring through Suzuki reaction. In the above reaction, the polarity of the aryl phosphinyloxy borate and the aromatic phosphinyloxy product may be similar, resulting in difficulty in separation; in addition, the hydrolysis product of the arylphosphinoxyboronic acid esters may form potential oligomeric condensation products which are detrimental to isolation and purification.
Disclosure of Invention
In order to overcome the defects and shortcomings of the prior art, the primary purpose of the invention is to provide a preparation method of high-purity aromatic phosphine oxide compounds.
By means of arylphosphinoxyboronates
With halogenated aromatic hydrocarbon or halogenated heteroaromatic hydrocarbon Br-R 2 The coupling reaction of (a) can conveniently give aryl-containing phosphinyloxy functional compounds (formula I,/-)>
). The invention provides a method for converting residual aryl phosphineoborate and boric acid derivatives thereof into corresponding phenol derivatives by the synergistic effect of peroxide oxidant and alkali, thereby achieving the purification aim.
It is another object of the present invention to provide the high purity aromatic phosphine oxide compound prepared by the above method.
The aim of the invention is achieved by the following scheme:
the preparation method of the high-purity aromatic phosphine oxide compound comprises the following steps:
wherein X is Cl, br or I;
R 1 and R is 2 Is aryl, heteroaryl, substituted aryl or substituted heteroaryl;
m=1-6; when m is more than or equal to 2, R 1 May be the same or different; br-R 2 Less polar than the aromatic phosphine oxide product (formula I);
the R is 1 Is any one of the following representative structural units:
wherein R is 3 And R4 is alkyl, aryl, heteroaryl, substituted aryl, and substituted heteroaryl, or may form a cyclic structure.
The R is 2 Aryl and heteroaryl, substituted or unsubstituted, are any of the following representative structural units:
wherein R is 5 Is a substituted or unsubstituted aryl or heteroaryl group.
The preparation method comprises the following steps:
(1) With diphenyl (monohaloaryl) phosphines
The diphenyl (monobromoaryl) phosphine oxide intermediate +.>
(2) Diphenyl (monobromoaryl) phosphine oxide obtained in step (1)
Obtaining diphenyl aryl phosphine oxide borate intermediate s through palladium catalyzed boric acid esterification;
(3) Diphenyl aryl phosphine oxide borate obtained in step (2)
With bromoaryl derivatives Br-R 2 Obtaining aryl phosphine oxide compound by Suzuki coupling reaction>
Is a crude product of (a).
(4) Separating the crude product obtained in the step (3) by flash column chromatography to remove Br-R 2 ；
(5) Removing Br-R from the solution obtained in step (4) 2 The product of (2) contains aryl phosphine oxide compound, which is dissolved in organic solvent, and peroxide oxidant/alkali is added to convert residual aryl phosphine oxide boric acid ester and boric acid derivative thereof into corresponding phenol derivative;
(6) Further post-treatment processes including column chromatography, solvent washing, recrystallization and sublimation are adopted to obtain the high-purity aromatic phosphine oxide compound.
Preferably, the molar ratio of diphenyl (monobromoaryl) phosphine to hydrogen peroxide in the step (1) is 1:3-6.
Preferably, the coupling reaction in step (2) is a Suzuki coupling reaction after mixing diphenyl (monobromoaryl) phosphine oxide with a palladium catalyst and pinacol biborate.
Preferably, the molar ratio of diphenyl (monobromoaryl) phosphine oxide to palladium catalyst and bisboronic acid pinacol ester is 1: 0.01-0.03:1-3.
Preferably, the molar ratio of diphenyl aryl phosphine oxide borate to bromoaryl derivative in step (3) is 1:1 to 1.3.
Preferably, the temperature of the Suzuki coupling reaction in the step (3) is 70-100 ℃, and the reaction time is 1-24 hours.
Preferably, the column chromatography eluent in the step (4) is dichloromethane or toluene, a mixed solvent of xylene and ethyl acetate, methanol, ethanol and isopropanol.
Preferably, the specific process in step (5) is: br-R will be removed 2 After which the peroxide oxidizing agent is added and stirred, followed by the alkali solution.
Preferably, the organic solvent in the step (5) is a mixed solvent of dichloromethane and alcohol, and the alcohol is at least one of ethanol, methanol and isopropanol.
Preferably, the molar ratio of the aryl phosphine oxide containing compound to the peroxide oxidizing agent in step (5) is 1:1-20.
Preferably, the molar ratio of peroxide oxidant to base in step (5) is from 1:1 to 20.
Preferably, the peroxide oxidizing agent used in step (5) is hydrogen peroxide, sodium peroxide, potassium peroxide, di-t-butyl peroxide, peracetic acid, benzoyl peroxide, or the like.
Preferably, the base used in step (5) is a hydroxide, such as sodium hydroxide, potassium hydroxide.
Preferably, the column chromatography eluent in the step (6) is dichloromethane or toluene, a mixed solvent of xylene and ethyl acetate, methanol, ethanol and isopropanol.
Preferably, the sublimation in the step (6) is purification by sublimation at a gradient temperature, and the gradient sublimation temperature ranges from 150 ℃ to 300 ℃ and from 250 ℃ to 400 ℃.
Compared with the prior art, the invention has the following advantages:
(1) The invention discloses a purification preparation method of aryl phosphine oxide compound, which converts residual aryl phosphine oxide boric acid ester and boric acid derivatives thereof into corresponding phenol derivatives, thereby achieving the purpose of separation and purification;
(2) The invention discloses a purification preparation method of aryl phosphine oxide compound, which uses the synergistic effect of peroxide oxide and strong alkali to biologically quantitatively convert aryl phosphine oxide boric acid ester and boric acid derivative thereof into corresponding phenol derivative, wherein the conversion yield reaches or approaches to 100%;
(3) The purification preparation method provided by the invention can realize large-scale synthesis of high-purity aryl phosphine oxide compounds.
Drawings
FIG. 1 is an ESI-MS mass spectrum of 3- (diphenylphosphinoyl) phenol;
FIG. 2 is a nuclear magnetic spectrum of an arylphosphine oxide PO1 after purification and refining in an embodiment of the invention, wherein the solvent is deuterated dichloromethane;
FIG. 3 is an HPLC chart of compound PO1 after purification and refinement;
FIG. 4 is a nuclear magnetic spectrum of an arylphosphine oxide PO2 after purification and refining in an embodiment of the invention, wherein the solvent is deuterated dimethyl sulfoxide;
FIG. 5 is a HPLC chromatogram of Compound PO2 after purification and refinement;
FIG. 6 is a nuclear magnetic spectrum of an aryl phosphine oxide compound PO3 after purification and refining in an embodiment of the invention, wherein the solvent is deuterated dimethyl sulfoxide;
FIG. 7 is an HPLC chromatogram of Compound PO3 after purification and refinement;
FIG. 8 is a nuclear magnetic resonance spectrum of an arylphosphine oxide PO4 after purification and refining in an embodiment of the invention, wherein the solvent is deuterated dichloromethane;
FIG. 9 is a HPLC chart of compound PO4 after purification and refinement;
FIG. 10 is a nuclear magnetic resonance spectrum of an arylphosphine oxide PO5 after purification and refining in an embodiment of the invention, wherein the solvent is deuterated dichloromethane;
FIG. 11 is an HPLC chromatogram of Compound PO5 after purification.
Detailed Description
The present invention will be described in further detail with reference to examples and drawings, but embodiments of the present invention are not limited thereto. The specific conditions are not noted in the examples and are carried out according to conventional conditions or conditions recommended by the manufacturer. The reagents or apparatus used were conventional products commercially available without the manufacturer's attention.
Experimental exploration process:
diphenyl [3- (4, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) phenyl ]]Phosphine oxide (100 mg,0.25 mmol) was dissolved in dichloromethane (30 mL), and aqueous hydrogen peroxide (15 eq.3.75 mmol) and ethanol (1 mL) were added and stirred at room temperature. Subsequently, an aqueous sodium hydroxide solution (45 eq.3 m) was further added thereto. Thereupon, no "diphenyl [3- (4, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) phenyl" could be detected by TLC]Phosphine oxide). Stopping the reaction, adding sodium bisulphite aqueous solution, quenching excessive hydrogen peroxide, extracting with dichloromethane, collecting an organic layer, and back-extracting with water; the obtained organic layer was dried over anhydrous magnesium sulfate, filtered, the solvent was distilled off under reduced pressure and separated by column chromatography, and the eluent was a mixed solvent of methylene chloride and ethanol (100:1 v/v), to give 3- (diphenylphosphono) phenol (69 mg) as a white solid in 95% yield. HRMS (ESI, negative ion mode) M/z: [ M-H ] + ] - :C 18 H 14 O 2 Calculated value of P: 293.0731; experimental values: 293.0756 (100%).
Dichloromethane: ethanol (100:1 v/v) as a developing agent, diphenyl [3- (4, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) phenyl ] phosphine oxide had an Rf value of 0.3, while 3- (diphenylphosphono) phenol had an Rf value reduced to 0.05.TLC detection showed conversion of the aryl phosphinoxyborate to the corresponding phenol derivative and increased polarity, mainly due to the strong electron withdrawing effect of the p=o group.
FIG. 1 is an ESI-MS mass spectrum (anion pattern) of 3- (diphenylphosphinoyl) phenol.
The five compounds prepared by the purification preparation method in the invention have the following chemical formulas:
example 1
The specific synthetic procedure for the compound PO1 described in this example 1 is as follows:
step one preparation of (3-bromophenyl) diphenylphosphine oxide (Compound 1)
To a solution of (3-bromophenyl) diphenylphosphine (12.3 g,36 mmol) in methylene chloride (60 mL) was added hydrogen peroxide (15 mL) and ethanol (15 mL). The reaction was stirred at room temperature overnight. After the reaction was completed, an aqueous sodium sulfite solution was poured into the reaction mixture to reduce an excessive amount of hydrogen peroxide. Then, the organic layer is firstly extracted by methylene dichloride and then back extracted by water; the obtained organic layer was dried over anhydrous magnesium sulfate, filtered, the solvent was distilled off under reduced pressure and separated by column chromatography, and the eluent was a mixed solvent of dichloromethane and ethanol to obtain a white solid in 97% yield (12.5 g).
1 H NMR(400MHz,DMSO)δ7.86(d,J＝7.8Hz,1H),7.74(d,J＝11.7Hz,1H),7.49–7.67(m,12H)。
Step two preparation of diphenyl (3- (4, 5-tetramethyl-1, 3, 2-dioxaborane-2-yl) phenyl) phosphine oxide (Compound 2)
At N 2 Under the atmosphere, the [1,1' -bis (diphenylphosphino) ferrocene]Palladium dichloride (254 mg,0.35 mmol) was added to a reaction solution of (3-bromophenyl) diphenylphosphine oxide (12.5 g,35 mmol), pinacol biborate (10.6 g,42 mmol), potassium acetate (10.3 g,105 mmol) and 1, 4-dioxane (200 mL) obtained in the step one, and the reaction was heated to 80 ℃. After 12 hours of reaction, the mixture was cooled to room temperature, the solvent was evaporated under reduced pressure, and then extracted with dichloromethane and water. The collected organic layer is back extracted with water, dried over anhydrous magnesium sulfate, filtered, the solvent is removed by distillation under reduced pressure, and the eluent is dichloromethane and ethanolThe solvents were mixed to give a white solid in 95% yield (13.4 g).
1 H NMR(400MHz,DMSO)δ8.08(d,J＝11.8Hz,1H),7.90(dd,J＝7.3,1.3Hz,1H),7.53–7.66(m,12H),1.28(s,12H)。
Step three, preparation of Compound PO1
At N 2 Tetrakis (triphenylphosphine) palladium (29 mg,0.0247 mmol) was added to a reaction solution of 9-bromo-10- (4- (phenanthr-9-yl) phenyl) anthracene (1.6 g,3.21 mmol), diphenyl (3- (4, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) phenyl) phosphine oxide (1 g,2.47 mmol), sodium carbonate aqueous solution (2 m,7.41 mmol), toluene (40 mL), ethanol (9 mL) under an atmosphere. The reaction was heated to 90 ℃ and stirred overnight. After cooling to room temperature, water was added, the organic layer was separated and back-extracted with water. The obtained organic layer was dried over anhydrous magnesium sulfate, filtered, the solvent was distilled off under reduced pressure and separated by column chromatography, and gradient elution was performed, with the eluent being methylene chloride (removal of 9-bromo-10- (4- (phenanthr-9-yl) phenyl) anthracene), a mixed solvent of methylene chloride and ethanol (100:1 v/v) in this order. For the sample separated by column chromatography, or further washing with an alcoholic solvent, a white solid (1.19 g) was obtained.
1 H NMR(500MHz,Methylene Chloride-d 2 Fig. 2) δ8.86 (dd, j=8.4, 1.3hz, 1H), 8.80 (d, j=8.2 hz, 1H), 8.21 (dd, j=8.2, 1.3hz, 1H), 8.01 (dd, j=7.7, 1.5hz, 1H), 7.97-7.86 (m, 4H), 7.83-7.53 (m, 19H), 7.50 (m, 4H), 7.45-7.37 (m, 4H).
Step four: purification and refining process of compound PO1
(1) The chemical treatment process comprises the following steps: the crude product obtained by column chromatography in the above step three was dissolved in methylene chloride (100 mL), and an aqueous hydrogen peroxide solution (1 eq.) and ethanol (5 mL) were added thereto and stirred at room temperature. Subsequently, an aqueous sodium hydroxide solution (3 eq.3M) was added thereto, and stirring was continued for 30 minutes. The excess hydrogen peroxide was quenched by addition of aqueous sodium bisulfite. Then extracting by using dichloromethane, collecting an organic layer, and carrying out back extraction by using water; the obtained organic layer was dried over anhydrous magnesium sulfate, filtered, and the solvent was distilled off under reduced pressure, followed by separation by column chromatography with a mixed solvent of methylene chloride and ethanol (100:1 v/v) as an eluent to obtain a white solid. Dissolving the product obtained by column chromatography in dichloromethane, adding ethanol to precipitate solid, heating, stirring, refluxing for 12 hr, filtering while hot, and drying to obtain filter cake.
Dichloromethane: ethanol (100:1 v/v) was used as a developing agent, and 3- (diphenylphosphono) phenol had an Rf value of about 0.05 and PO1 had an Rf value of 0.25, thereby effecting column chromatography separation.
(2) And (5) sublimation and purification. The filter cake obtained was subjected to gradient temperature sublimation. The HPLC purity of PO1 was 99.94% (FIG. 3).
Example 2
The specific synthetic procedure for the compound PO2 described in this example 2 is as follows:
the procedure for the preparation of example 1 was the same as for diphenyl (3- (4, 5-tetramethyl-1, 3, 2-dioxaborane-2-yl) phenyl) phosphine oxide in example 2.
Step one, preparation of a compound PO 2:
at N 2 Tetrakis (triphenylphosphine) palladium (114 mg,0.0985 mmol) was charged into a three-necked flask with diphenyl- (3- (4, 5-tetramethyl-1, 3, 2-dioxan-2-yl) phenyl) phosphine oxide (3.98 g,9.85 mmol), 2- (3- (10-bromoanthracene-9-yl) phenyl) -4, 6-diphenyl-1, 3, 5-triazine (6.66 g,11.8 mmol), 200mL of toluene was added and 15mL of aqueous sodium hydroxide solution (2M), followed by 15mL of ethanol, and the mixture was stirred at 90 ℃ for reaction for 12 hours; after cooling to room temperature, water was added, the organic layer was separated and back-extracted with water. The obtained organic layer was dried over anhydrous magnesium sulfate, filtered, the solvent was distilled off under reduced pressure and separated by column chromatography, and the eluent was methylene chloride (removing residual 2- (3- (10-bromoanthracene-9-yl) phenyl) -4, 6-diphenyl-1, 3, 5-triazine), a mixed solvent of methylene chloride and ethanol (100:1 v/v); washing the sample separated by column chromatography or further using alcohol solvent to obtain white solidCompound PO2, 55% yield (4.1 g).
1 H NMR(500MHz,DMSO-d 6 Fig. 4) δ8.73-8.64 (m, 4H), 7.96 (m, 1H), 7.93-7.86 (m, 2H), 7.85-7.74 (m, 6H), 7.71-7.56 (m, 17H), 7.51-7.44 (m, 4H).
Step two: purification and refining process of compound PO 2:
(1) The chemical treatment process comprises the following steps: the crude product obtained by column chromatography in the above step one was dissolved in methylene chloride (100 mL), and an aqueous hydrogen peroxide solution (1 eq.) and ethanol (5 mL) were added thereto and stirred at room temperature. Subsequently, an aqueous sodium hydroxide solution (3 eq.3 m) was added thereto, and stirring was continued. When TLC detects the absence of borate starting material, the reaction is stopped. The excess hydrogen peroxide was quenched by addition of aqueous sodium bisulfite. Then extracting by using dichloromethane, collecting an organic layer, and back extracting by using water; the obtained organic layer was dried over anhydrous magnesium sulfate, filtered, the solvent was distilled off under reduced pressure and separated by column chromatography, and the eluent was a mixed solvent of dichloromethane and ethanol (100:1 v/v), to obtain pale yellow solid. Dissolving the product obtained by column chromatography in dichloromethane, adding ethanol to precipitate solid, heating, stirring, refluxing for 12 hr, filtering while hot, and drying to obtain filter cake.
Dichloromethane: ethanol (100:1 v/v) was used as a developing agent, and 3- (diphenylphosphono) phenol had an Rf value of about 0.05 and PO2 had an Rf value of 0.25, thereby effecting column chromatography separation.
(2) And (5) sublimation and purification. And (3) carrying out gradient temperature sublimation on the obtained filter cake to obtain a product. The HPLC purity of PO2 was 99.95% (fig. 5).
Example 3
The specific synthetic procedure for the compound PO3 described in this example 3 is as follows:
diphenyl (3- (4, 5-tetramethyl-1, 3, 2-dioxaborane-2-yl) phenyl) phosphine oxide in this example 3 was prepared in the same manner as in example 1.
Step one, preparation of a compound PO 3:
at N 2 Tetrakis (triphenylphosphine) palladium (12 mg) was added to a toluene (30 ml) mixture of diphenyl (3- (4, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) phenyl) phosphine oxide (405 mg,1.001 mmol), 2- (3-bromophenyl) -4, 6-diphenyl-1, 3, 5-triazine (505 mg,1.300 mmol), ethanol (4 ml) and sodium carbonate aqueous solution (2 m,4 ml) under an atmosphere, and reacted under stirring at 90 ℃ for 12 hours; after cooling to room temperature, water was added, the organic layer was separated and back-extracted with water. The obtained organic layer is dried by anhydrous magnesium sulfate, filtered, the solvent is removed by reduced pressure distillation and column chromatography is carried out, and the eluent is methylene dichloride (residual 2- (3-bromophenyl) -4, 6-diphenyl-1, 3, 5-triazine is removed), and a mixed solvent of methylene dichloride and ethanol (100:1v/v); for the sample isolated by column chromatography, or further washing with an alcoholic solvent, the compound PO3 was obtained as a white solid in 70% yield (412 mg).
1 H NMR (500 MHz, DMSO-d6 FIG. 6) delta 8.82 (t, J=1.8 Hz, 1H), 8.73 (m, 5H), 8.08 (m, 1H), 8.01-7.90 (m, 2H), 7.81-7.70 (m, 9H), 7.70-7.63 (m, 6H), 7.63-7.57 (m, 4H). HPLC = 99.95%
Step two: purification and refining process of compound PO 3:
(1) The chemical treatment process comprises the following steps: the crude product obtained by column chromatography in the above step one was dissolved in methylene chloride (100 mL), and an aqueous hydrogen peroxide solution (1 eq.) and ethanol (5 mL) were added thereto and stirred at room temperature. Subsequently, an aqueous sodium hydroxide solution (3 eq.3 m) was added thereto, and stirring was continued. When TLC detects the absence of borate starting material, the reaction is stopped. The excess hydrogen peroxide was quenched by addition of aqueous sodium bisulfite. Then extracting by using dichloromethane, collecting an organic layer, and back extracting by using water; the obtained organic layer was dried over anhydrous magnesium sulfate, filtered, the solvent was distilled off under reduced pressure and separated by column chromatography, and the eluent was a mixed solvent of dichloromethane and ethanol (100:1 v/v), to obtain a white solid. Dissolving the product obtained by column chromatography in dichloromethane, adding isopropanol to the dichloromethane to precipitate solid, heating, stirring and refluxing for 12h, filtering while the product is hot, and drying the obtained filter cake.
Dichloromethane: ethanol (100:1 v/v) was used as a developing agent, and 3- (diphenylphosphono) phenol had an Rf value of about 0.05 and PO2 had an Rf value of 0.25, thereby effecting column chromatography separation.
(2) And (5) sublimation and purification. And (3) carrying out gradient temperature sublimation on the sample obtained in the step one to obtain a product. The HPLC purity of PO3 was 99.95% (fig. 7).
Example 4
The specific synthetic procedure for the compound PO4 described in this example 4 is as follows:
the procedure for the preparation of example 1 was the same as for diphenyl (3- (4, 5-tetramethyl-1, 3, 2-dioxaborane-2-yl) phenyl) phosphine oxide in example 4.
Step one, preparation of Compound PO4
Pd (PPh) 3 ) 4 (33 mg,0.029 mmol) was added rapidly to a mixture of 3-bromo-9-phenyl-6- (9-phenylcarbazol-3-yl) carbazole (1.71 g,3.03 mmol), diphenyl (3- (4, 5-dioxaborane-2-yl) phenyl) phosphine oxide (1.17 g,2.89 mmol) and potassium carbonate (2M, 8.67 mmol) in toluene (100 mL) and ethanol (25 mL), heated to 90℃and reacted overnight. After cooling to room temperature, water was added, the organic layer was separated and back-extracted with water. The obtained organic layer is dried by anhydrous magnesium sulfate, filtered, the solvent is removed by reduced pressure distillation and column chromatography separation are carried out, and the eluent is dichloromethane (residual 3-bromo-9-phenyl-6- (9-phenylcarbazole-3-yl) carbazole is removed), and a mixed solvent of dichloromethane and ethanol (100:1v/v) is adopted; 1.85g (84%) of a white solid was obtained.
1 H NMR(500MHz,Methylene Chloride-d 2 Fig. 8) δ8.53 (d, j=1.7hz, 1H), 8.52-8.49 (m, 1H), 8.47 (d, j=1.8hz, 1H), 8.25 (m, 1H), 8.15 (m, 1H), 7.96 (m, 1H), 7.82 (m, 2H), 7.75-7.69 (m, 4H), 7.68-7.61 (m, 10H), 7.60-7.55 (m, 3H), 7.54-7.47 (m, 11H), 7.46-7.40 (m, 2H), 7.31 (m, 1H).
Step two: purification and refining process of compound PO 4:
(1) The chemical treatment process comprises the following steps: the crude product obtained by column chromatography was dissolved in methylene chloride (100 mL), and an aqueous hydrogen peroxide solution (1 eq.) and ethanol (5 mL) were added thereto and stirred at room temperature. Subsequently, an aqueous sodium hydroxide solution (3 eq.3 m) was added thereto, and stirring was continued. When TLC detects the absence of borate starting material, the reaction is stopped. The excess hydrogen peroxide was quenched by addition of aqueous sodium bisulfite. Then extracting by using dichloromethane, collecting an organic layer, and back extracting by using water; the obtained organic layer was dried over anhydrous magnesium sulfate, filtered, the solvent was distilled off under reduced pressure and separated by column chromatography, and the eluent was a mixed solvent of dichloromethane and ethanol (100:1 v/v), to obtain a white solid. Dissolving the product obtained by column chromatography in dichloromethane, adding isopropanol to the dichloromethane to precipitate solid, heating, stirring and refluxing for 12h, filtering while the product is hot, and drying the obtained filter cake.
Dichloromethane: ethanol (100:1 v/v) was used as a developing agent, and 3- (diphenylphosphono) phenol had an Rf value of about 0.05 and PO2 had an Rf value of 0.25, thereby effecting column chromatography separation.
(2) And (5) sublimation and purification. And (3) carrying out gradient temperature sublimation on the obtained filter cake to obtain a product. The HPLC purity of PO4 was 99.97% (fig. 9).
Example 5
The specific synthetic procedure for the compound PO5 described in this example 5 is as follows:
preparation of (2-bromo-9, 9' -spirobifluorene-7-yl) diphenylphosphine oxide (Compound 3)
To a solution of (2-bromo-9, 9' -spirobifluorene-7-yl) diphenylphosphine (4.86 g,8.4 mmol) in dichloromethane (60 mL) was added hydrogen peroxide (15 mL) and ethanol (15 mL). The reaction was stirred at room temperature overnight. After the reaction was completed, an aqueous sodium sulfite solution was poured into the reaction mixture to reduce an excessive amount of hydrogen peroxide. Then, the organic layer is firstly extracted by methylene dichloride and then back extracted by water; the obtained organic layer was dried over anhydrous magnesium sulfate, filtered, the solvent was distilled off under reduced pressure and separated by column chromatography, and the eluent was a mixed solvent of dichloromethane and ethanol to obtain a white solid in 97% yield (4.85 g).
1 H NMR(400MHz,CD 2 Cl 2 )δ7.89(dd,J＝10.1,2.2Hz,1H),7.85(d,J＝7.6Hz,2H),7.79(d,J＝8.2Hz,1H),7.55-7.48(m,8H),7.42-7.36(m,6H),7.19(d,J＝11.48Hz,1H),7.14(dd,J＝8.2,7.6Hz,2H),6.86(d,J＝1.8Hz,1H),6.71(d,J＝5.5Hz,2H)。
Preparation of diphenyl (2- (4, 5-tetramethyl-1, 3, 2-dioxaborane-2-yl) -9,9' -spirobifluorene-7-yl) phosphine oxide (Compound 4)
At N 2 Under the atmosphere, the [1,1' -bis (diphenylphosphino) ferrocene]Palladium dichloride (37 mg,0.05 mmol) was added to a reaction solution of 2-bromo-9, 9' -spirobifluorene-7-yl) diphenylphosphine oxide (3 g,5.05 mmol), pinacol biborate (1.54 g,6.06 mmol), potassium acetate (1.48 g,15.15 mmol), 1, 4-dioxane (100 mL) obtained in step one, and the reaction was heated to 80 ℃. After 12 hours of reaction, the mixture was cooled to room temperature, the solvent was evaporated under reduced pressure, and then extracted with dichloromethane and water. The collected organic layer was back-extracted with water, dried over anhydrous magnesium sulfate, filtered, the solvent was distilled off under reduced pressure and separated by column chromatography, and the eluent was a mixed solvent of dichloromethane and ethanol to give a white solid in 83.56% (2.71 g).
1 H NMR(500MHz,CD 2 Cl 2 )δ7.95-7.92(m,2H),7.87(d,J＝7.7Hz,2H),7.53(dd,J＝7.7,0.9Hz,1H),7.53-7.47(m,7H),7.42-7.37(m,6H),7.20(d,J＝11.7Hz,1H),7.14(m,2H),7.06(s,1H),6.69(d,J＝7.6Hz,2H),1.23(s,12H)。
Step three, preparation of Compound PO5
At N 2 Palladium acetate (0.036, 8 mg), tricyclohexylphosphine (0.14 mmol,39 mg) were added to diphenyl (2- (4, 5-tetramethyl-1, 3, 2-dioxaborane-2-yl) -9,9' -spirobifluorene-7-yl) phosphine oxide (2.5 g,3.89 mmol), 3-bromo-1, 10-phenanthroline (1 g,3.54 mmol), sodium carbonate aqueous solution (2M, 23.6 mmol), toluene (200 mL), ethanol (50 mL) of the reaction mixture. The reaction was heated to 90 ℃ and stirred overnight. After cooling to room temperature, water was added, the organic layer was separated and back-extracted with water. The obtained organic layer was dried over anhydrous magnesium sulfate, filtered, the solvent was distilled off under reduced pressure and separated by column chromatography, and gradient elution was performed, the eluent was a mixed solvent (100:1 v/v) of dichloromethane and ethanol in this order (residual diphenyl (2- (4, 5-tetramethyl-1, 3, 2-dioxaborane-2-yl) -9,9' -spirobifluorene was removed)]-7-yl) phosphine oxide), a mixed solvent of methylene chloride and ethanol (50: 1 v/v) (removal of residual 3-bromo-1, 10-phenanthroline), a mixed solvent of dichloromethane and ethanol (20: 1 v/v). For the sample isolated by column chromatography, or further washing with ethyl acetate, alcohol solvents, a white solid (1.12 g, 42%) was obtained.
1 H NMR(500MHz,Methylene Chloride-d 2 Fig. 10) δ9.29 (d, j=2.3 hz, 1H), 9.14 (dd, j=4.3, 1.7hz, 1H), 8.28 (dd, j=8.9, 2.3hz, 2H), 8.15 (d, j=7.95 hz, 1H), 8.03 (dd, j=7.8, 2.5hz, 1H), 7.96-7.92 (m, 3H), 7.81 (dd, j=15.3, 8.9hz, 2H), 7.65 (dd, j=8.1, 4.3hz, 1H), 7.59-7.54 (m, 7H), 7.47-7.42 (m, 6H), 7.28 (d, j=11.6 hz, 1H), 7.23-7.19 (m, 3H), 6.84 (d, j=7.7 hz, 2H).
Step four: purification and refining process of compound PO5
(1) The chemical treatment process comprises the following steps: the crude product obtained by the three-column chromatography was dissolved in methylene chloride (100 mL), and an aqueous hydrogen peroxide solution (1 eq.) and ethanol (5 mL) were added and stirred at room temperature. Subsequently, an aqueous sodium hydroxide solution (3 eq.3 m) was further added thereto. After stirring for 30min, an aqueous solution of sodium bisulphite was added and the excess hydrogen peroxide quenched. Then extracting by using dichloromethane, collecting an organic layer, and back extracting by using water; the obtained organic layer was dried over anhydrous magnesium sulfate, filtered, the solvent was distilled off under reduced pressure and separated by column chromatography, and the eluent was a mixed solvent of dichloromethane and ethanol (50:1 v/v), a mixed solvent of dichloromethane and ethanol (20:1 v/v) in this order, to obtain a white solid.
Dichloromethane: ethanol (100:1 v/v) as a developing agent, 3- (diphenylphosphono) phenol having an Rf value of 0.05 and PO5 maintained substantially at the origin; when methylene dichloride: the mixing ratio of ethanol was raised to 20:1v/v, with the Rf value of 3- (diphenylphosphono) phenol being 0.8 and the Rf value of PO5 being 0.2. The polarity of 3- (diphenylphosphono) phenol should be similar to that of 7- (diphenylphosphono) - (9, 9' -spirobifluorene) -2-phenol, thereby achieving column chromatographic separation.
(2) And (5) sublimation and purification. And (3) carrying out gradient temperature sublimation on the obtained filter cake to obtain a product. The HPLC purity of PO5 was 99.96% (fig. 11).
The above examples are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above examples, and any other changes, modifications, substitutions, combinations, and simplifications that do not depart from the spirit and principle of the present invention should be made in the equivalent manner, and the embodiments are included in the protection scope of the present invention.
Claims (10)
1. The preparation method of the high-purity aromatic phosphine oxide compound is characterized by comprising the following steps of:
wherein X is Cl, br or I;
R 1 and R is 2 Is aryl, heteroaryl, substituted aryl or substituted heteroaryl;
m=1-6; when m is more than or equal to 2, R 1 May be the same or different; br-R 2 Is less polar than the aromatic phosphine oxide product, as in formula I,
formula I:
2. the method for preparing a high purity aromatic phosphine oxide compound according to claim 1, comprising the steps of:
(1) Takes diphenyl (monohalogenated aryl) phosphine as raw material
By dioxygenOxidation with water gives the diphenyl (monobromoaryl) phosphine oxide intermediate +.>
(2) Diphenyl (monobromoaryl) phosphine oxide obtained in step (1)
Obtaining diphenyl aryl phosphine oxide borate intermediate by palladium catalyzed boric acid esterification>
(3) Diphenyl aryl phosphine oxide borate obtained in step (2)
With bromoaryl derivatives Br-R 2 Obtaining aryl phosphine oxide compound by Suzuki coupling reaction>
Is a crude product of (2);
(4) Separating the crude product obtained in the step (3) by flash column chromatography to remove Br-R 2 ；
(5) Removing Br-R from the solution obtained in step (4) 2 The product of (2) contains aryl phosphine oxide compound, which is dissolved in organic solvent, and peroxide oxidant/alkali is added to convert residual aryl phosphine oxide boric acid ester and boric acid derivative thereof into corresponding phenol derivative;
(6) Further post-treatment processes including column chromatography, solvent washing, recrystallization and sublimation are adopted to obtain the high-purity aryl-containing phosphine oxide compound.
3. The method for preparing the high-purity aromatic phosphine oxide compound according to claim 2, wherein the method comprises the following steps:
the molar ratio of diphenyl (monobromoaryl) phosphine to hydrogen peroxide in the step (1) is 1:3-6.
4. The method for preparing the high-purity aromatic phosphine oxide compound according to claim 2, wherein the method comprises the following steps:
the coupling reaction in the step (2) is that diphenyl (monobromoaryl) phosphine oxide is mixed with a palladium catalyst and bisboronic acid pinacol ester and then subjected to a Suzuki coupling reaction;
the molar ratio of the diphenyl (monobromoaryl) phosphine oxide to the palladium catalyst and the bisboronic acid pinacol ester is 1: 0.01-0.03:1-3.
5. The method for preparing the high-purity aromatic phosphine oxide compound according to claim 2, wherein the method comprises the following steps:
the molar ratio of diphenyl aryl phosphine oxide borate to bromoaryl derivative in step (3) is 1:1 to 1.3;
the temperature of the Suzuki coupling reaction in the step (3) is 70-100 ℃, and the reaction time is 1-24 h.
6. The method for preparing the high-purity aromatic phosphine oxide compound according to claim 2, wherein the method comprises the following steps:
the column chromatography eluent in the step (4) is dichloromethane or toluene, a mixed solvent of xylene and ethyl acetate, methanol, ethanol and isopropanol.
7. The method for preparing the high-purity aromatic phosphine oxide compound according to claim 2, wherein the method comprises the following steps:
the specific process in the step (5) is as follows: br-R will be removed 2 Dissolving the coupling product of (a) in an organic solvent, then adding a peroxide oxidant, stirring, and then adding an alkali solution, stirring;
the organic solvent in the step (5) is a mixed solvent of dichloromethane and alcohol, and the alcohol is at least one of ethanol, methanol and isopropanol.
8. The process for producing a high-purity aromatic phosphine oxide compound according to claim 2 or 7, wherein:
the molar ratio of the aryl phosphine oxide-containing compound to the peroxide oxidant in the step (5) is 1:1-20;
the molar ratio of the peroxide oxidant to the alkali in the step (5) is 1:1-20.
9. The process for producing a high-purity aromatic phosphine oxide compound according to claim 2 or 7, wherein:
the peroxide oxidant adopted in the step (5) is at least one of hydrogen peroxide, sodium peroxide, potassium peroxide, di-tert-butyl peroxide, peracetic acid and benzoyl peroxide;
the alkali adopted in the step (5) is at least one of hydroxide, sodium hydroxide and potassium hydroxide.
10. The method for preparing the high-purity aromatic phosphine oxide compound according to claim 2, wherein the method comprises the following steps:
the column chromatography eluent in the step (6) is dichloromethane or toluene, a mixed solvent of xylene and ethyl acetate, methanol, ethanol and isopropanol;
sublimation in the step (6) is purification by gradient temperature sublimation, wherein the gradient sublimation temperature ranges from 150 ℃ to 300 ℃ and from 250 ℃ to 400 ℃.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211692535.0A CN116396327A (en) | 2022-12-28 | 2022-12-28 | Preparation method of high-purity aromatic phosphine oxide compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211692535.0A CN116396327A (en) | 2022-12-28 | 2022-12-28 | Preparation method of high-purity aromatic phosphine oxide compound |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN116396327A true CN116396327A (en) | 2023-07-07 |
Family
ID=87014853
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202211692535.0A Pending CN116396327A (en) | 2022-12-28 | 2022-12-28 | Preparation method of high-purity aromatic phosphine oxide compound |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN116396327A (en) |
-
2022
- 2022-12-28 CN CN202211692535.0A patent/CN116396327A/en active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101180302B (en) | Process for preparing (alpha s, beta r)-6-bromo-alpha-[2-(dimethylamino)ethyl]-2-methoxy-alpha-1-naphthalenyl-beta-phenyl-3-quinolineethanol | |
| KR20130129180A (en) | Process for preparing aminobenzoylbenzofuran derivatives | |
| CN112174989B (en) | Preparation method of clenbuterol | |
| WO2016043462A2 (en) | Method for preparing calcobutrol | |
| CN110183445B (en) | Synthetic method of moxifloxacin and derivatives thereof | |
| CN114539149A (en) | Compound containing isoquinoline ring, preparation method and application thereof | |
| WO2000062782A1 (en) | Novel synthesis and crystallization of piperazine ring-containing compounds | |
| CN116396327A (en) | Preparation method of high-purity aromatic phosphine oxide compound | |
| CN107814757B (en) | Method for synthesizing polysubstituted pyrrole derivative | |
| CN111468183A (en) | Polyfluoro triaryl chiral spiro phosphoric acid catalyst, and preparation method and application thereof | |
| CN116332991A (en) | Purification preparation method of aryl phosphine oxide group-containing compound | |
| CN114213424A (en) | Synthetic method of furan [3, 2-b ] pyridine derivative | |
| CN114989154A (en) | Raltitrexed dimer impurity, synthesis method and application thereof | |
| JP3938413B2 (en) | Process for producing organophosphorus compounds | |
| CN107935913B (en) | Carbazole compound and synthesis method and application thereof | |
| CN100408577C (en) | Process for the preparation of imidazo(1,2-A)pyridine-3-acetamides | |
| KR20140071474A (en) | Methods for the preparation of 5-[2-[7-(trifluoromethyl)-5-[4-(trifluoromethyl)phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]ethynyl]-2-pyridinamine | |
| KR100805198B1 (en) | New preparation method of 10-(2,5-dihydroxyphenyl-9,10-dihydro-9-oxa-phosphaphenanthrene-10-oxide | |
| CN116589475B (en) | Preparation method of 2',4',5',7' -tetrachloro-5 (6) -carboxyl-4, 7-dichloro fluorescein | |
| CN113416142B (en) | Preparation method of 5-ALA intermediate 5-bromolevulinate | |
| CN115010656B (en) | Preparation method of 5-acetyl-2-bromopyridine | |
| CN109810036B (en) | Synthesis method of 4-oxo-5- (arylformyl acetate-2-yl) naphthalene-sulfoxide ylide hybrid | |
| CN109369600B (en) | Synthesis method of 2-substituted methylene aromatic ring benzopyran compound | |
| CN109265311B (en) | Phenyl fluorene derivative and preparation method and application thereof | |
| KR101856586B1 (en) | Preparation method of 13-Bromo-10H-phenanthro[9,10-b]carbazole |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |