CN110372746A - A method of synthesis beta-amido phosphine oxide compound - Google Patents
A method of synthesis beta-amido phosphine oxide compound Download PDFInfo
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- CN110372746A CN110372746A CN201910623792.0A CN201910623792A CN110372746A CN 110372746 A CN110372746 A CN 110372746A CN 201910623792 A CN201910623792 A CN 201910623792A CN 110372746 A CN110372746 A CN 110372746A
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- 238000000034 method Methods 0.000 title claims abstract description 31
- 238000003786 synthesis reaction Methods 0.000 title abstract description 6
- 230000015572 biosynthetic process Effects 0.000 title description 5
- 238000006243 chemical reaction Methods 0.000 claims abstract description 39
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims abstract description 28
- -1 amido phosphine oxide compound Chemical class 0.000 claims abstract description 27
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims abstract description 24
- 150000001336 alkenes Chemical class 0.000 claims abstract description 24
- 229910000033 sodium borohydride Inorganic materials 0.000 claims abstract description 19
- 239000012279 sodium borohydride Substances 0.000 claims abstract description 19
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims abstract description 18
- 238000007445 Chromatographic isolation Methods 0.000 claims abstract description 11
- 238000011097 chromatography purification Methods 0.000 claims abstract description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 6
- 238000002390 rotary evaporation Methods 0.000 claims abstract description 6
- 238000005913 hydroamination reaction Methods 0.000 claims abstract description 5
- 230000007717 exclusion Effects 0.000 claims abstract description 4
- 239000007795 chemical reaction product Substances 0.000 claims abstract description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 3
- 239000011521 glass Substances 0.000 claims description 14
- 230000002194 synthesizing effect Effects 0.000 claims description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 6
- OTEKOJQFKOIXMU-UHFFFAOYSA-N 1,4-bis(trichloromethyl)benzene Chemical compound ClC(Cl)(Cl)C1=CC=C(C(Cl)(Cl)Cl)C=C1 OTEKOJQFKOIXMU-UHFFFAOYSA-N 0.000 claims 1
- 125000001476 phosphono group Chemical group [H]OP(*)(=O)O[H] 0.000 claims 1
- 238000006722 reduction reaction Methods 0.000 claims 1
- 239000003054 catalyst Substances 0.000 abstract description 4
- 239000002994 raw material Substances 0.000 abstract description 3
- 229910052723 transition metal Inorganic materials 0.000 abstract description 3
- 150000003624 transition metals Chemical class 0.000 abstract description 3
- 238000003912 environmental pollution Methods 0.000 abstract description 2
- 239000000047 product Substances 0.000 description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- CCSWAGCMVMYGIC-UHFFFAOYSA-N ethyl acetate;pyridine;hydrate Chemical compound O.CCOC(C)=O.C1=CC=NC=C1 CCSWAGCMVMYGIC-UHFFFAOYSA-N 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 239000002253 acid Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- 238000005654 Michaelis-Arbuzov synthesis reaction Methods 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000010959 commercial synthesis reaction Methods 0.000 description 1
- 238000005260 corrosion Methods 0.000 description 1
- 230000007797 corrosion Effects 0.000 description 1
- PMJARSVDFGNNRI-UHFFFAOYSA-N dichloromethane;piperidine Chemical compound ClCCl.C1CCNCC1 PMJARSVDFGNNRI-UHFFFAOYSA-N 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 125000001477 organic nitrogen group Chemical group 0.000 description 1
- HBGWPRXYTQMRMA-UHFFFAOYSA-N oxolane;pyridine;hydrate Chemical compound O.C1CCOC1.C1=CC=NC=C1 HBGWPRXYTQMRMA-UHFFFAOYSA-N 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/576—Six-membered rings
- C07F9/59—Hydrogenated pyridine rings
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
Abstract
The present invention provides a kind of synthesisβThe method of amido phosphine oxide compound, especially room temperature are condition, and hydroamination reaction occurs with diphenylphosphino connection alkene and hexahydropyridine, then reacts and generates under the reaction condition of sodium borohydrideβAmido phosphine oxide compound.Diphenylphosphino connection alkene is added in reactor, anhydrous methylene chloride is added, adds hexahydropyridine；By the air in reactor exclusion system, carry out reaction in the environment of nitrogen；The reactor connected is reacted at room temperature；Reaction product through TLC determine diphenylphosphino connection alkene oneself it is reacted completely after, be added sodium borohydride the reaction was continued 12-15 hours with trifluoroacetic acid, rotary evaporation in vacuo, column chromatographic isolation and purification to get.Inventive process avoids the uses of transition-metal catalyst, improve the spatter property of synthetic reaction, reduce environmental pollution；Two step of the method for the present invention is completed, and the raw material type used is single, improves the economy of technique.
Description
Technical field
The invention belongs to technical field of medicine synthesis, are related to a kind of method for synthesizing beta-amido phosphine oxide compound, especially
Under the conditions of room temperature is without transition-metal catalyst, using diphenylphosphino connection alkene and hexahydropyridine as Material synthesis beta-amido phosphine oxygen
The method of compound.
Background technique
Beta-amido phosphine oxide compound is a kind of important fine chemicals, medicine intermediate and material intermediate, is had good
Good biological activity can be used as antibacterial agent and AntiHIV1 RT activity reagent etc..At the same time, beta-amido phosphine oxide compound has good
Coordination ability be a kind of important organic nitrogen phosphorus ligand.β-hexahydropyridine base hexichol phosphono compound molecular formula is
C20H26ONP, relative molecular mass 327.4.Belong to beta-amido phosphine oxide compound, chemical structural formula are as follows:
At present, β-carbonyl phosphine oxide compound synthetic method mainly includes Arbuzov reaction, under strong acid or basic conditions
The acylation reaction of phosphonate ester, and the condition of these reactions is often harsher, strong acid and strong base severe corrosion equipment, simultaneously
Environmental-friendly, Atom economy theory is not met.With the development of environmental economy, need development environment it is more friendly, it is low at
This method.
Under room temperature without transition-metal catalyst more clean it is green, energy saving, reduce cost, while it is nonmetallic
The use of reagent can reduce metal reagent bring cost and pollution problem.
Summary of the invention
In order to overcome the drawbacks of the prior art, the present invention provides a kind of method for synthesizing beta-amido phosphine oxide compound, the party
Method have many advantages, such as it is environmentally protective, energy saving, reduce cost.
Diphenylphosphino joins alkene and hydroamination reaction occurs for hexahydropyridine, then anti-under the reaction condition of sodium borohydride
Beta-amido phosphine oxide compound should be generated.
For achieving the above object, with diphenylphosphino connection alkene and hexahydropyridine hydroamination reaction occurs for the present invention,
Then reaction generates beta-amido phosphine oxide compound under the reaction condition of sodium borohydride.
Specifically, the present invention the following steps are included:
(1) diphenylphosphino connection alkene is added in reactor, anhydrous methylene chloride is added, adds hexahydropyridine.
(2) by the air in glass reactor and exclusion system, carry out reaction in the environment of nitrogen.
(3) reactor connected is reacted at room temperature；
(4) reaction product through TLC determine diphenylphosphino connection alkene oneself it is reacted completely after, sodium borohydride and trifluoro is added
The reaction was continued 12-15 hours for acetic acid, rotary evaporation in vacuo, column chromatographic isolation and purification to get.
Wherein:
By the molar ratio of diphenylphosphino connection alkene and hexahydropyridine in step (1) are as follows: (1:1-1:2)
The 3-5mL of methylene chloride in step (1)
Room temperature in step (3) is 25-30 degree；
Sodium borohydride (2.5mmol), trifluoroacetic acid (2.0mmol), mole of sodium borohydride and trifluoroacetic acid in step (4)
Than the molar ratio 2.5:2:1 for 2.5:2, with sodium borohydride, trifluoroacetic acid and raw material
The solvent of thin-layer chromatography described in step (4) is ethyl acetate
The method of the present invention has the advantages that significant compared with traditional handicraft.Main feature has: (1) the method for the present invention reacts item
Part is mildly simple, improves the spatter property of commercial synthesis reaction, reduces environmental pollution.(2) the method for the present invention is used without making
With catalyst, reduce costs.(3) two step of the method for the present invention is completed, and the raw material type used is single, improves the economy of technique
Property.(4) the method for the present invention may be selected to complete reaction under room temperature, normal pressure.Reaction, which can reduce, under room temperature, normal pressure sets reaction
Standby requirement reduces consersion unit manufacturing cost and reaction process cost, improves the safety of reaction.(5) method of the invention
The beta-amido phosphine oxide compound yield of preparation is up to 70% or more, and purity is up to 90% or more.
Specific embodiment
A kind of method of synthesis beta-amido phosphine oxide compound of the invention, comprising the following steps:
1. diphenylphosphino connection alkene is added in reactor, anhydrous solvent is added, adds hexahydropyridine.Wherein solvent
For anhydrous methanol；Glass reaction bottle can be used in laboratory in reactor, and glass tank reactor can be used in when industrial production
Or tubular reactor etc.；Temperature of reactor is set as 25 DEG C or so；Diphenylphosphino joins alkene and the molar ratio of hexahydropyridine is
1:2。
2. by the air in glass reactor and exclusion system.
3. the reactor after connection is reacted at room temperature 12 hours.Sodium borohydride is then added, and the reaction was continued with trifluoroacetic acid
12 hours, rotary evaporation in vacuo, column chromatographic isolation and purification calculate the productivity and yield of beta-amido phosphine oxide compound.
Specific embodiment:
Process in detail is come with specific embodiment below, embodiment does not represent the invention scope of limitation this patent.
Embodiment 1
In 25mL glass reaction bottle, 0.5mol diphenylphosphino is added and joins alkene, 3mL anhydrous methylene chloride is added
0.5mol hexahydropyridine reacts 12 hours.Rotary evaporation in vacuo, column chromatographic isolation and purification, beta-amido phosphine oxide compound yield 0.
Embodiment 2
In 25mL glass reaction bottle, 0.5mol diphenylphosphino joins alkene, and 0.5mol is added in 3mL anhydrous methylene chloride
Hexahydropyridine reacts 12 hours.The reaction was continued 12 hours for addition 2.5mol sodium borohydride and 2.0mol trifluoroacetic acid.Vacuum rotating
Evaporation, column chromatographic isolation and purification, product are beta-amido phosphine oxide compound, yield 50%.
Embodiment 3
In 25mL glass reaction bottle, 0.5mol diphenylphosphino joins alkene, and 1mol six is added in 3mL anhydrous methylene chloride
Pyridinium hydroxide reacts 12 hours.The reaction was continued 12 hours for addition 2.5mol sodium borohydride and 2.0mol trifluoroacetic acid.Vacuum rotating steams
Hair, column chromatographic isolation and purification, product are beta-amido phosphine oxide compound, yield 70%.
Embodiment 4
In 25mL glass reaction bottle, 0.5mol diphenylphosphino joins alkene, and 1mol six is added in 3mL anhydrous tetrahydro furan
Pyridinium hydroxide reacts 12 hours.The reaction was continued 12 hours for addition 2.5mol sodium borohydride and 2.0mol trifluoroacetic acid.Vacuum rotating steams
Hair, column chromatographic isolation and purification, product are beta-amido phosphine oxide compound, yield 58%.
Embodiment 5
In 25mL glass reaction bottle, 0.5mol diphenylphosphino joins alkene, and 1mol six is added in 3mL anhydrous ethyl acetate
Pyridinium hydroxide reacts 12 hours.The reaction was continued 12 hours for addition 2.5mol sodium borohydride and 2.0mol trifluoroacetic acid.Vacuum rotating steams
Hair, column chromatographic isolation and purification, product are beta-amido phosphine oxide compound, yield 64%.
Embodiment 6
In 25mL glass reaction bottle, 0.5mol diphenylphosphino joins alkene, and 1mol six is added in 3mL anhydrous methylene chloride
Pyridinium hydroxide reacts 12 hours.2.5mol sodium borohydride is added, and the reaction was continued 12 hours.Rotary evaporation in vacuo, column chromatography for separation are pure
Change, product is beta-amido phosphine oxide compound, yield 34%.
Embodiment 7
In 25mL glass reaction bottle, 0.5mol diphenylphosphino joins alkene, and 1mol six is added in 3mL anhydrous ethyl acetate
Pyridinium hydroxide reacts 12 hours.The reaction was continued 12 hours for addition 2.5mol sodium borohydride and 1.0mol trifluoroacetic acid.Vacuum rotating steams
Hair, column chromatographic isolation and purification, product are beta-amido phosphine oxide compound, yield 48%.
Embodiment 8
In 25mL glass reaction bottle, 0.5mol diphenylphosphino joins alkene, and 1mol six is added in 3mL anhydrous ethyl acetate
Pyridinium hydroxide reacts 12 hours.The reaction was continued 12 hours for addition 2.0mol sodium borohydride and 2.0mol trifluoroacetic acid.Vacuum rotating steams
Hair, column chromatographic isolation and purification, product are beta-amido phosphine oxide compound, yield 50%.
It should be understood that for those of ordinary skills, it can be modified or changed according to the above description,
And all these modifications and variations should all belong to the protection domain of appended claims of the present invention.
Claims (10)
1. a kind of method for synthesizing beta-amido phosphine oxide compound, which is characterized in that join alkene and hexahydropyridine with diphenylphosphino
Hydroamination reaction occurs, then reaction generates beta-amido phosphine oxide compound under the reaction condition of sodium borohydride.
2. a kind of method for synthesizing beta-amido phosphine oxide compound according to claim 1, which is characterized in that diphenyl phosphono
Base join alkene and hexahydropyridine hydroamination reaction occurs the following steps are included:
(1) diphenylphosphino connection alkene is added in reactor, anhydrous methylene chloride is added, adds hexahydropyridine；
(2) by the air in reactor exclusion system, carry out reaction in the environment of nitrogen；
(3) reactor connected is reacted at room temperature；
(4) reaction product through TLC determine diphenylphosphino connection alkene oneself it is reacted completely after, sodium borohydride and trifluoroacetic acid is added
The reaction was continued 12-15 hours, rotary evaporation in vacuo, column chromatographic isolation and purification to get.
3. a kind of method for synthesizing beta-amido phosphine oxide compound according to claim 2, which is characterized in that the step
(1) anhydrous methylene chloride is 3-5 milliliters in.
4. a kind of method for synthesizing beta-amido phosphine oxide compound according to claim 2, which is characterized in that the hexichol
Base phosphono joins alkene and hexahydropyridine molar ratio is 1:1-1:2.
5. a kind of method for synthesizing beta-amido phosphine oxide compound according to claim 2, which is characterized in that in step (3)
Reaction temperature be 25-30 degree.
6. a kind of method for synthesizing beta-amido phosphine oxide compound according to claim 2, which is characterized in that step (4) institute
The thin layer condition of the TLC stated are as follows: ethyl acetate.
7. a kind of method for synthesizing beta-amido phosphine oxide compound according to claim 2, which is characterized in that in step (4)
The sodium borohydride dosage 95mg.
8. a kind of method for synthesizing beta-amido phosphine oxide compound according to claim 2, which is characterized in that the trifluoro
228 milligrams of acetic acid dosage.
9. a kind of method for synthesizing beta-amido phosphine oxide compound according to claim 2, which is characterized in that the reactor
For simple glass reaction flask, or have glass tank reactor or tubular reactor.
10. it is according to claim 2 it is a kind of synthesize beta-amido phosphine oxide compound method, which is characterized in that reactor in
Step (1) aminating reaction 12-15 hours, step (2) reduction reaction 12-15 hours.
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Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101115746A (en) * | 2005-02-18 | 2008-01-30 | 阿皮德公开股份有限公司 | Novell processes for the preparation of a benzofuran |
| CN102675268A (en) * | 2012-05-18 | 2012-09-19 | 济南志合医药科技有限公司 | Method for preparing (1R,2R)-2-(2,3-dihydrobenzofuran-4-yl) cyclopropanemethylamine |
| CN103058912A (en) * | 2012-12-28 | 2013-04-24 | 山东邹平大展新材料有限公司 | Preparation method of 3-(4-chlorobutyl)indole-5-formonitrile |
| CN103304466A (en) * | 2013-05-18 | 2013-09-18 | 嘉兴中科化学有限公司 | Synthetic method of 3-alkyl-substituted indole compound |
| CN104892356A (en) * | 2015-05-08 | 2015-09-09 | 常州市阳光药业有限公司 | Preparation method for 3-(trifluoromethyl)benzenepropanol |
| CN108341768A (en) * | 2018-03-12 | 2018-07-31 | 成都平和安康医药科技有限公司 | A kind of method that reduction method prepares vitamin B6 |
-
2019
- 2019-07-11 CN CN201910623792.0A patent/CN110372746A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101115746A (en) * | 2005-02-18 | 2008-01-30 | 阿皮德公开股份有限公司 | Novell processes for the preparation of a benzofuran |
| CN102675268A (en) * | 2012-05-18 | 2012-09-19 | 济南志合医药科技有限公司 | Method for preparing (1R,2R)-2-(2,3-dihydrobenzofuran-4-yl) cyclopropanemethylamine |
| CN103058912A (en) * | 2012-12-28 | 2013-04-24 | 山东邹平大展新材料有限公司 | Preparation method of 3-(4-chlorobutyl)indole-5-formonitrile |
| CN103304466A (en) * | 2013-05-18 | 2013-09-18 | 嘉兴中科化学有限公司 | Synthetic method of 3-alkyl-substituted indole compound |
| CN104892356A (en) * | 2015-05-08 | 2015-09-09 | 常州市阳光药业有限公司 | Preparation method for 3-(trifluoromethyl)benzenepropanol |
| CN108341768A (en) * | 2018-03-12 | 2018-07-31 | 成都平和安康医药科技有限公司 | A kind of method that reduction method prepares vitamin B6 |
Non-Patent Citations (3)
| Title |
|---|
| FRANCISCO PALACIOS ET AL.: "Synthesis of Secondary E-Allylamines and β-Aminophosphorylated Compounds from β-Functionalized Enamines Derived from Phosphonium Salts, Phosphine Oxides and Phosphonates", 《TETRAHEDRON》 * |
| JOHN M. SWAN ET AL.: "Organophosphorus Compounds. XVI* 2-(N-Dialkylamino)alkyldiphenylphosphines, Phosphine Oxides and Sulphides as Analogues of Methadone", 《AUST. J. CHEM.》 * |
| LI-HENG RUAN ET AL.: "Base-promoted synthesis of β-ketophosphine oxides from diphenylphosphorylallenes", 《ASIAN J. ORG. CHEM》 * |
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