CN112028935A - Preparation method of vinyl phosphonate - Google Patents
Preparation method of vinyl phosphonate Download PDFInfo
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- CN112028935A CN112028935A CN202010978251.2A CN202010978251A CN112028935A CN 112028935 A CN112028935 A CN 112028935A CN 202010978251 A CN202010978251 A CN 202010978251A CN 112028935 A CN112028935 A CN 112028935A
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- vinyl phosphonate
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- reaction
- ethyl acetate
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- ZTWTYVWXUKTLCP-UHFFFAOYSA-L ethenyl-dioxido-oxo-$l^{5}-phosphane Chemical compound [O-]P([O-])(=O)C=C ZTWTYVWXUKTLCP-UHFFFAOYSA-L 0.000 title claims abstract description 50
- 238000002360 preparation method Methods 0.000 title claims abstract description 35
- 238000006243 chemical reaction Methods 0.000 claims abstract description 22
- -1 aryl ethylene Chemical compound 0.000 claims abstract description 20
- 238000000034 method Methods 0.000 claims abstract description 20
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims abstract description 18
- 229910000024 caesium carbonate Inorganic materials 0.000 claims abstract description 18
- 239000003960 organic solvent Substances 0.000 claims abstract description 13
- JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical compound C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 claims abstract description 13
- 239000005977 Ethylene Substances 0.000 claims abstract description 11
- XRBCRPZXSCBRTK-UHFFFAOYSA-N phosphonous acid Chemical compound OPO XRBCRPZXSCBRTK-UHFFFAOYSA-N 0.000 claims abstract description 11
- 230000001681 protective effect Effects 0.000 claims abstract description 9
- 239000002994 raw material Substances 0.000 claims abstract description 7
- 239000012298 atmosphere Substances 0.000 claims abstract description 6
- 238000010438 heat treatment Methods 0.000 claims abstract description 6
- 238000002156 mixing Methods 0.000 claims abstract description 6
- 238000003756 stirring Methods 0.000 claims abstract description 6
- 230000035484 reaction time Effects 0.000 claims abstract description 5
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 63
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 24
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 18
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 16
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 15
- 238000001035 drying Methods 0.000 claims description 15
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 12
- 238000004440 column chromatography Methods 0.000 claims description 12
- 239000012074 organic phase Substances 0.000 claims description 12
- 239000003208 petroleum Substances 0.000 claims description 12
- 239000000203 mixture Substances 0.000 claims description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 9
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 9
- 239000003480 eluent Substances 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
- 238000000926 separation method Methods 0.000 claims description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 9
- 239000007789 gas Substances 0.000 claims description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims description 8
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 6
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 6
- 150000001875 compounds Chemical class 0.000 claims description 6
- 125000001624 naphthyl group Chemical class 0.000 claims description 6
- 229910052786 argon Inorganic materials 0.000 claims description 5
- 238000001816 cooling Methods 0.000 claims description 5
- HNULCUYNXDDQCB-UHFFFAOYSA-M 1,2-dimethylpyridin-1-ium;iodide Chemical compound [I-].CC1=CC=CC=[N+]1C HNULCUYNXDDQCB-UHFFFAOYSA-M 0.000 claims description 3
- GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 125000005059 halophenyl group Chemical group 0.000 claims description 3
- 239000011259 mixed solution Substances 0.000 claims description 3
- ABFPKTQEQNICFT-UHFFFAOYSA-M 2-chloro-1-methylpyridin-1-ium;iodide Chemical compound [I-].C[N+]1=CC=CC=C1Cl ABFPKTQEQNICFT-UHFFFAOYSA-M 0.000 claims 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical class C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims 1
- 125000003609 aryl vinyl group Chemical group 0.000 claims 1
- 150000003222 pyridines Chemical class 0.000 claims 1
- 239000003054 catalyst Substances 0.000 abstract description 16
- 239000007800 oxidant agent Substances 0.000 abstract description 7
- 230000001590 oxidative effect Effects 0.000 abstract description 7
- 230000000694 effects Effects 0.000 abstract description 4
- 239000000758 substrate Substances 0.000 abstract description 3
- 230000002411 adverse Effects 0.000 abstract description 2
- 239000002904 solvent Substances 0.000 abstract description 2
- 239000000126 substance Substances 0.000 abstract description 2
- 239000012043 crude product Substances 0.000 description 6
- 238000006546 Horner-Wadsworth-Emmons reaction Methods 0.000 description 4
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- 238000000605 extraction Methods 0.000 description 4
- 239000012299 nitrogen atmosphere Substances 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 230000003197 catalytic effect Effects 0.000 description 3
- KLTIMEXKPRJOIS-UHFFFAOYSA-N 2-chloro-1-methyl-2H-pyridine hydroiodide Chemical compound I.CN1C=CC=CC1Cl KLTIMEXKPRJOIS-UHFFFAOYSA-N 0.000 description 2
- JLBJTVDPSNHSKJ-UHFFFAOYSA-N 4-Methylstyrene Chemical compound CC1=CC=C(C=C)C=C1 JLBJTVDPSNHSKJ-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- BQMQLJQPTQPEOV-UHFFFAOYSA-N OP(=O)OC=C Chemical class OP(=O)OC=C BQMQLJQPTQPEOV-UHFFFAOYSA-N 0.000 description 2
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical group C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 2
- LSXWFXONGKSEMY-UHFFFAOYSA-N di-tert-butyl peroxide Chemical compound CC(C)(C)OOC(C)(C)C LSXWFXONGKSEMY-UHFFFAOYSA-N 0.000 description 2
- JJPBKCZJVYSKGV-UHFFFAOYSA-N diethoxyphosphane Chemical compound CCOPOCC JJPBKCZJVYSKGV-UHFFFAOYSA-N 0.000 description 2
- KTLIMPGQZDZPSB-UHFFFAOYSA-M diethylphosphinate Chemical compound CCP([O-])(=O)CC KTLIMPGQZDZPSB-UHFFFAOYSA-M 0.000 description 2
- XQRLCLUYWUNEEH-UHFFFAOYSA-L diphosphonate(2-) Chemical compound [O-]P(=O)OP([O-])=O XQRLCLUYWUNEEH-UHFFFAOYSA-L 0.000 description 2
- 239000002360 explosive Substances 0.000 description 2
- 239000003999 initiator Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 229910052759 nickel Inorganic materials 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- ACVYVLVWPXVTIT-UHFFFAOYSA-M phosphinate Chemical compound [O-][PH2]=O ACVYVLVWPXVTIT-UHFFFAOYSA-M 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 229910052703 rhodium Inorganic materials 0.000 description 2
- 239000010948 rhodium Substances 0.000 description 2
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- DDOQBQRIEWHWBT-VKHMYHEASA-N (2S)-2-amino-4-phosphonobutanoic acid Chemical compound OC(=O)[C@@H](N)CCP(O)(O)=O DDOQBQRIEWHWBT-VKHMYHEASA-N 0.000 description 1
- CORMBJOFDGICKF-UHFFFAOYSA-N 1,3,5-trimethoxy 2-vinyl benzene Natural products COC1=CC(OC)=C(C=C)C(OC)=C1 CORMBJOFDGICKF-UHFFFAOYSA-N 0.000 description 1
- KTZVZZJJVJQZHV-UHFFFAOYSA-N 1-chloro-4-ethenylbenzene Chemical compound ClC1=CC=C(C=C)C=C1 KTZVZZJJVJQZHV-UHFFFAOYSA-N 0.000 description 1
- PDELBHCVXBSVPJ-UHFFFAOYSA-N 2-ethenyl-1,3,5-trimethylbenzene Chemical compound CC1=CC(C)=C(C=C)C(C)=C1 PDELBHCVXBSVPJ-UHFFFAOYSA-N 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 229910002567 K2S2O8 Inorganic materials 0.000 description 1
- 238000006845 Michael addition reaction Methods 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 150000001345 alkine derivatives Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- QPKOILOWXGLVJS-UHFFFAOYSA-N bis(2-methylpropoxy)-oxophosphanium Chemical compound CC(C)CO[P+](=O)OCC(C)C QPKOILOWXGLVJS-UHFFFAOYSA-N 0.000 description 1
- 150000001717 carbocyclic compounds Chemical class 0.000 description 1
- 208000015114 central nervous system disease Diseases 0.000 description 1
- 150000001879 copper Chemical class 0.000 description 1
- FKRCVWBISKAAPX-UHFFFAOYSA-N di(propan-2-yloxy)phosphane Chemical compound CC(C)OPOC(C)C FKRCVWBISKAAPX-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000003063 flame retardant Substances 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000006292 intramolecular Alder-ene reaction Methods 0.000 description 1
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- GDOPTJXRTPNYNR-UHFFFAOYSA-N methyl-cyclopentane Natural products CC1CCCC1 GDOPTJXRTPNYNR-UHFFFAOYSA-N 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- 125000001476 phosphono group Chemical group [H]OP(*)(=O)O[H] 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- ZTWTYVWXUKTLCP-UHFFFAOYSA-N vinylphosphonic acid Chemical class OP(O)(=O)C=C ZTWTYVWXUKTLCP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/40—Esters thereof
- C07F9/4003—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
- C07F9/4056—Esters of arylalkanephosphonic acids
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
- B01J31/0234—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds
- B01J31/0235—Nitrogen containing compounds
- B01J31/0244—Nitrogen containing compounds with nitrogen contained as ring member in aromatic compounds or moieties, e.g. pyridine
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/26—Catalysts comprising hydrides, coordination complexes or organic compounds containing in addition, inorganic metal compounds not provided for in groups B01J31/02 - B01J31/24
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Inorganic Chemistry (AREA)
Abstract
The invention provides a preparation method of vinyl phosphonate, which is characterized by comprising the following steps: adding aryl ethylene and phosphonite serving as raw materials into a first organic solvent under the atmosphere of protective gas, then adding cesium carbonate and pyridinium, fully stirring and uniformly mixing the system, then heating, and reacting at 50-100 ℃ to obtain the vinyl phosphonate. The method does not need to use an oxidant, avoids the adverse effect of strong chemical properties of the oxidant on the preparation process, and improves the safety of the reaction. By using the bi-component catalysts cesium carbonate and pyridinium, the yield and purity of the target product can be improved under the condition of small using amount, the reaction time is short, and the catalyst has a considerable effect on different substrates, solvents and the like and has good universality.
Description
Technical Field
The invention relates to the field of organic synthesis, in particular to a preparation method of vinyl phosphonate and application of a bi-component catalyst in catalytic preparation of vinyl phosphonate.
Background
The vinylphosphonate compounds are organic synthesis intermediates with wide application range, and can be used for synthesizing biological activity
Sex molecules, flame retardants, and polymer additives, among others. The vinylphosphonate compound is also widely applied to Michael addition reaction, namely Horner-Wadsworth-Emmons reaction, so that various target compounds are synthesized. The vinylphosphonate compound can also be applied to intramolecular Ene reaction and continuous Ene and Wittig-Horner ring-closing reaction so as to produce a carbocyclic compound. The vinylphosphonate compound can also generate hetero Dies-Alder reaction, and the addition product of the vinylphosphonate compound generally has high stereospecificity
And regioselectivity, and the range of the substituent group carried by the reactant is wide, so the method is widely applied. Meanwhile, the vinylphosphonate compound can also be used as a precursor of an effective medicament L-AP4 for treating central nervous diseases such as Parkinson's disease, Alzheimer's disease and the like. Therefore, the development of an organic synthesis method for efficiently synthesizing the vinylphosphonate compound plays an important role.
At present, the following are mainly used for vinyl phosphonate compounds:
(1) the tetraalkoxy diphosphonate reacts with aldehyde or ketone by Wittig-Horner reaction to obtain vinyl phosphonate or tetraalkoxy diphosphonate, firstly, the vinyl phosphonate is acylated at the alpha position of phosphono group, and then Wittig-Horner reaction is carried out to prepare the vinyl phosphonate, but the reaction needs to be carried out at the extremely harsh reaction temperature of-78 ℃ because n-butyl lithium is used as a catalyst, and the operation is not easy.
(2) The catalyst is prepared by taking alkyne and phosphonite as raw materials and reacting with catalysts such as palladium, rhodium, nickel and the like, and the catalyst uses noble metal catalysts such as palladium, rhodium, nickel and the like, so that the synthesis process has higher cost and is not beneficial to industrial development.
(3) QingwenGui et al (chem. Commun. 2015,51,13922-2S2O8The method adopts TEMPO as an initiator to prepare the vinyl phosphonate compound at the temperature of 100 ℃, adopts a catalyst, the oxidant and the initiator simultaneously, has complex system components, and adopts an oxidant K2S2O8The method is flammable and explosive, has larger potential safety hazard, and has low yield of the final product of 55-81%.
(4) Chinese patent CN 106674277A discloses a method for preparing vinyl phosphonate compounds, which uses aryl ethylene and phosphonite as raw materials, adopts ferric trichloride and copper salt as catalysts and di-tert-butyl peroxide as an oxidant, and adopts high-temperature reaction, wherein the di-tert-butyl peroxide used in the method is inflammable and explosive, the overall yield is 25-82%, the yield is not high, and the yield is greatly influenced by factors such as substrates, catalysts, temperature and the like, so that the yield is unstable, and the industrial development is not facilitated.
Disclosure of Invention
Based on solving the above problems, the present invention provides a method for preparing vinyl phosphonate, which is characterized by comprising the following steps: adding aryl ethylene and phosphonite serving as raw materials into a first organic solvent under the atmosphere of protective gas, then adding cesium carbonate and pyridinium, fully stirring and uniformly mixing the system, then heating, and reacting at 50-100 ℃ to obtain the vinyl phosphonate.
According to the preparation method of the vinyl phosphonate, the aryl ethylene has a structure of a compound shown as a formula I
Wherein Ar is selected from the group consisting of phenyl, halophenyl, alkyl-substituted phenyl, naphthyl, halonaphthyl, alkyl-substituted naphthyl; the structure of the phosphonite is a compound of a formula II
Wherein R is selected from alkyl.
According to the preparation method of the vinylphosphonate, in the formula I, Ar is selected from phenyl substituted by C1-C6 alkyl.
According to the preparation method of the vinyl phosphonate, in the formula II, R is selected from C1-C6 alkyl.
According to the preparation method of the vinylphosphonate, the protective gas is nitrogen or argon.
According to the preparation method of the vinyl phosphonate ester, the protective gas is preferably nitrogen.
According to the preparation method of the vinyl phosphonate, the feeding molar ratio of the aryl ethylene to the phosphinate to the cesium carbonate to the pyridinium is 1: 1-3: 0.05-0.1, and the reaction time is 2-5 hours.
According to the preparation method of the vinylphosphonate, the first organic solvent is selected from one or more of acetonitrile, toluene, DMSO or DMF.
The preparation method of the vinylphosphonate further comprises the following steps of cooling the system to room temperature after the reaction is finished, pouring the mixture into water, extracting by using a second organic solvent, taking an organic phase, drying by using anhydrous sodium sulfate, concentrating under reduced pressure, and separating by column chromatography to obtain the vinylphosphonate.
According to the preparation method of the vinylphosphonate, the organic solvent is selected from one or more of ethyl acetate, dichloromethane or chloroform.
According to the preparation method of the vinylphosphonate, the eluent used for column chromatography separation is a mixed solution of ethyl acetate and petroleum ether.
According to the preparation method of the vinyl phosphonate, the volume ratio of the ethyl acetate to the petroleum ether is preferably 3: 1.
According to the preparation method of the vinylphosphonate, the pyridinium is at least one of 2-chloro-1-methylpyridine iodide (CMPI) and 1, 2-dimethylpyridinium iodide (DMPI).
In addition, the invention also provides a new application of the bi-component catalyst cesium carbonate and pyridinium in the catalytic preparation of vinyl phosphonate.
The main contributions of the present invention with respect to the prior art are the following:
(1) the invention takes aryl ethylene and phosphonite as raw materials, and takes cesium carbonate and pyridinium as catalysts for reaction, and the invention belongs to an original invention, and no report related to the method exists in the prior art.
(2) The method does not need to use an oxidant, avoids the adverse effect of strong chemical properties of the oxidant on the preparation process, and improves the safety of the reaction.
(3) By using the bi-component catalysts cesium carbonate and pyridinium, the yield and purity of the target product can be improved under the condition of small using amount, the reaction time is short, and the catalyst has a considerable effect on different substrates, solvents and the like and has good universality.
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present disclosure more apparent, the technical solutions of the embodiments of the present disclosure will be clearly and completely described below. It is to be understood that the described embodiments are only a few embodiments of the present disclosure, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the described embodiments of the disclosure without any inventive step, are within the scope of protection of the disclosure.
Unless otherwise defined, technical or scientific terms used herein shall have the ordinary meaning as understood by one of ordinary skill in the art to which this disclosure belongs. The use of "first," "second," and similar terms in this disclosure is not intended to indicate any order, quantity, or importance, but rather is used to distinguish one element from another.
The invention provides a preparation method of vinyl phosphonate, which is characterized by comprising the following steps: adding aryl ethylene and phosphonite serving as raw materials into a first organic solvent under the atmosphere of protective gas, then adding cesium carbonate and pyridinium, fully stirring and uniformly mixing the system, then heating, and reacting at 50-100 ℃ to obtain the vinyl phosphonate.
According to the preparation method of the vinyl phosphonate, the aryl ethylene has a structure of a compound shown as a formula I
Wherein Ar is selected from the group consisting of phenyl, halophenyl, alkyl-substituted phenyl, naphthyl, halonaphthyl, alkyl-substituted naphthyl; the structure of the phosphonite is a compound of a formula II
Wherein R is selected from alkyl.
According to the preparation method of the vinylphosphonate, in the formula I, Ar is selected from phenyl substituted by C1-C6 alkyl.
According to the preparation method of the vinyl phosphonate, in the formula II, R is selected from C1-C6 alkyl.
According to the preparation method of the vinylphosphonate, the protective gas is nitrogen or argon.
According to the preparation method of the vinyl phosphonate ester, the protective gas is preferably nitrogen.
According to the preparation method of the vinyl phosphonate, the feeding molar ratio of the aryl ethylene to the phosphinate to the cesium carbonate to the pyridinium is 1: 1-3: 0.05-0.1, and the reaction time is 2-5 hours.
According to the preparation method of the vinylphosphonate, the first organic solvent is selected from one or more of acetonitrile, toluene, DMSO or DMF.
The preparation method of the vinylphosphonate further comprises the following steps of cooling the system to room temperature after the reaction is finished, pouring the mixture into water, extracting by using a second organic solvent, taking an organic phase, drying by using anhydrous sodium sulfate, concentrating under reduced pressure, and separating by column chromatography to obtain the vinylphosphonate.
According to the preparation method of the vinylphosphonate, the organic solvent is selected from one or more of ethyl acetate, dichloromethane or chloroform.
According to the preparation method of the vinylphosphonate, the eluent used for column chromatography separation is a mixed solution of ethyl acetate and petroleum ether.
According to the preparation method of the vinyl phosphonate, the volume ratio of the ethyl acetate to the petroleum ether is preferably 3: 1.
According to the preparation method of the vinylphosphonate, the pyridinium is at least one of 2-chloro-1-methylpyridine iodide (CMPI) and 1, 2-dimethylpyridinium iodide (DMPI).
In addition, the invention also provides a new application of the bi-component catalyst cesium carbonate and pyridinium in the catalytic preparation of vinyl phosphonate.
Example 1
Under the nitrogen atmosphere, 100mmol of phenyl ethylene and 150mmol of diisopropyl phosphonite are added into 30mL of DMSO, then 10mmol of cesium carbonate and 5mmol of CMPI are added, the system is fully stirred and uniformly mixed, then the temperature is raised to 100 ℃, the temperature is kept for reaction for 2 hours, after the reaction is finished, the system is cooled to room temperature, the mixture is poured into water, ethyl acetate is used for extraction (30mL multiplied by 3), an organic phase is taken, anhydrous sodium sulfate is used for drying, reduced pressure concentration is carried out, column chromatography separation is carried out on a crude product by using ethyl acetate and petroleum ether with the volume ratio of 3:1 as an eluent, and high-purity vinyl phosphonate is obtained after concentration and drying, and the yield is 90%.
Example 2
Adding 100mmol of phenyl ethylene and 300mmol of diethyl phosphonite into 45mL of acetonitrile under the nitrogen atmosphere, then adding 10mmol of cesium carbonate and 10mmol of CMPI, fully stirring and uniformly mixing the system, then heating to 50 ℃, keeping the temperature for reaction for 4 hours, cooling the system to room temperature after the reaction is finished, pouring the mixture into water, extracting by using ethyl acetate (30mL multiplied by 3), taking an organic phase, drying by using anhydrous sodium sulfate, concentrating under reduced pressure, performing column chromatography separation on the crude product by using ethyl acetate and petroleum ether with a volume ratio of 3:1 as an eluent, concentrating and drying to obtain high-purity vinyl phosphonate with the yield of 93%.
Example 3
Under the nitrogen atmosphere, 100mmol of p-methylstyrene and 200mmol of diethyl phosphinate are added into 40mL of toluene, 10mmol of cesium carbonate and 10mmol of CMPI are then added, the system is fully stirred and uniformly mixed, the temperature is raised to 100 ℃, the temperature is kept for reaction for 2 hours, after the reaction is finished, the system is cooled to room temperature, the mixture is poured into water, ethyl acetate is used for extraction (30mL multiplied by 3), an organic phase is taken, anhydrous sodium sulfate is used for drying, reduced pressure concentration is carried out, column chromatography separation is carried out on a crude product by using ethyl acetate and petroleum ether with the volume ratio of 3:1 as an eluent, and high-purity vinylphosphonate is obtained after concentration and drying, wherein the yield is 91%.
Example 4
Under the nitrogen atmosphere, 100mmol of p-methylstyrene and 100mmol of diisobutylphosphite are added into 30mL of toluene, then 5mmol of cesium carbonate and 10mmol of CMPI are added, the system is fully stirred and uniformly mixed, then the temperature is raised to 100 ℃, the temperature is kept for reaction for 5 hours, after the reaction is finished, the system is cooled to room temperature, the mixture is poured into water, ethyl acetate is used for extraction (30mL multiplied by 3), an organic phase is taken, anhydrous sodium sulfate is used for drying, reduced pressure concentration is carried out, the crude product is subjected to column chromatography separation by using ethyl acetate and petroleum ether with the volume ratio of 3:1 as eluent, and high-purity vinylphosphonate is obtained by concentration and drying, wherein the yield is 86%.
Example 5
Under the atmosphere of nitrogen, 100mmol of p-chlorostyrene and 200mmol of diethyl phosphinate are added into 40mL of toluene, 10mmol of cesium carbonate and 10mmol of DMPI are then added, the system is fully and uniformly stirred and mixed, then the temperature is raised to 100 ℃, the temperature is kept for reaction for 2 hours, after the reaction is finished, the system is cooled to room temperature, the mixture is poured into water, ethyl acetate is used for extraction (30mL multiplied by 3), an organic phase is taken, anhydrous sodium sulfate is used for drying, the pressure is reduced for concentration, the crude product is subjected to column chromatography separation by using ethyl acetate and petroleum ether with the volume ratio of 3:1 as eluent, and the high-purity vinyl phosphonate is obtained after concentration and drying, wherein the yield is 95%.
Example 6
Adding 100mmol of 2,4, 6-trimethylstyrene and 300mmol of diethyl phosphonite into 45mL of DMSO under the atmosphere of nitrogen, then adding 10mmol of cesium carbonate and 10mmol of DMPI, fully stirring and uniformly mixing the system, then heating to 100 ℃, keeping the temperature for reaction for 3h, after the reaction is finished, cooling the system to room temperature, pouring the mixture into water, extracting by using ethyl acetate (30mL multiplied by 3), taking an organic phase, drying by using anhydrous sodium sulfate, concentrating under reduced pressure, performing column chromatography separation on the crude product by using ethyl acetate and petroleum ether with the volume ratio of 3:1 as eluent, concentrating and drying to obtain high-purity vinyl phosphonate with the yield of 92%.
Finally, it should be noted that: it should be understood that the above examples are only for clearly illustrating the present invention and are not intended to limit the embodiments. Other variations and modifications will be apparent to persons skilled in the art in light of the above description. And are neither required nor exhaustive of all embodiments. And obvious variations or modifications of the invention may be made without departing from the scope of the invention.
Claims (10)
1. A preparation method of vinyl phosphonate is characterized by comprising the following steps: adding aryl ethylene and phosphonite serving as raw materials into a first organic solvent under the atmosphere of protective gas, then adding cesium carbonate and pyridinium, fully stirring and uniformly mixing the system, then heating, and reacting at 50-100 ℃ to obtain the vinyl phosphonate.
2. The method of claim 1, wherein the aryl vinyl phosphonate has the structure of formula I
Wherein Ar is selected from the group consisting of phenyl, halophenyl, alkyl-substituted phenyl, naphthyl, halonaphthyl, alkyl-substituted naphthyl; the structure of the phosphonite is a compound of a formula II
Wherein R is selected from alkyl.
3. The method of claim 2, wherein Ar is selected from C1-C6 alkyl substituted phenyl, and R is selected from C1-C6 alkyl.
4. The method of claim 1, wherein the protective gas is nitrogen or argon, preferably nitrogen.
5. The method for preparing vinyl phosphonate according to claim 1, wherein the feeding molar ratio of aryl ethylene, phosphonite, cesium carbonate and pyridine salt is 1: 1-3: 0.05-0.1, and the reaction time is 2-5 h.
6. The method of claim 1, wherein the first organic solvent is selected from one or more of acetonitrile, toluene, DMSO, and DMF.
7. The method according to claim 1, further comprising the steps of cooling the system to room temperature after the reaction is completed, pouring the mixture into water, extracting the mixture with a second organic solvent, collecting the organic phase, drying the organic phase with anhydrous sodium sulfate, concentrating the organic phase under reduced pressure, and separating the organic phase by column chromatography to obtain vinylphosphonate.
8. The method according to claim 7, wherein the organic solvent is one or more selected from ethyl acetate, dichloromethane and chloroform.
9. The method for preparing vinyl phosphonate according to claim 7, wherein the eluent used for the column chromatography separation is a mixed solution of ethyl acetate and petroleum ether, preferably, the volume ratio of ethyl acetate to petroleum ether is 3: 1.
10. The method according to any one of claims 1 to 9, wherein the pyridinium salt is at least one selected from the group consisting of 2-chloro-1-methylpyridinium iodide (CMPI) and 1, 2-dimethylpyridinium iodide (DMPI).
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| CAO, HAO-QIANG ET AL: "Direct Enamido C(sp2)-H Diphosphorylation Enabled by a PCET-Triggered Double Radical Relay: Access to gem-Bisphosphonates", 《CHEMISTRY - A EUROPEAN JOURNAL》 * |
| GU, JIAN ET AL: "Cu(I)/Fe(III)-Catalyzed C-P cross-coupling of styrenes with H-phosphine oxides: a facile and selective synthesis of alkenylphosphine oxides and β-ketophosphonates", 《ORGANIC & BIOMOLECULAR CHEMISTRY》 * |
| PENG, ZHIYUAN ET AL: "Regio- and Stereoselective Hydrophosphorylation of Ynamides: A Facile Approach to (Z)-β-Phosphor-Enamides", 《ADVANCED SYNTHESIS & CATALYSIS》 * |
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